Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1992 Sep
PMID:Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). 149 70

The syndromes of insulin resistance are a group of clinically diverse disorders, and our understanding of their molecular pathogenesis has advanced in parallel with our understanding of the structure of the insulin receptor and the mechanism of insulin action. The most straightforward progress has related to defining the role of both anti-receptor antibodies and mutations in the insulin receptor gene in causing these disorders. Despite this progress, the cause of severe target cell resistance in patients without defects in the receptor locus remains unknown, and we are limited in our ability to relate specific molecular defects in insulin signalling to in vivo phenotypes, such as those relating to growth and development and function of adipose tissue and muscle. Answers to these questions may ultimately be explained by the existence of multiple species of insulin receptors expressed in different tissues, brought about by alternative splicing and receptor hybrids, and by divergent pathways of insulin signalling with different consequences for specific tissues. The possibility that the insulin receptor and GLUT4 may be candidate genes for inherited insulin resistance in NIDDM has been addressed with the aid of genetic screening techniques such as SSCP. Currently, the loci have not been implicated in studies in most patients. Transgenic methodologies will be powerful tools for pursuit of unanswered questions in the field of insulin resistance in coming years.
Diabetes 1992 Sep
PMID:Lilly Lecture: syndromes of insulin resistance. From patient to gene and back again. 149 71

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
 ...
PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

OBJECTIVE--To investigate the relationship between asymptomatic hyperglycemia (IGT or newly diagnosed NIDDM) and atherosclerotic vascular disease. RESEARCH DESIGN AND METHODS--A representative cross-sectional population sample of 1431 subjects (511 men, 920 women; 65-74 yr old). Altogether, 312 men and 515 women had NGT, 84 men and 158 women had IGT, 33 men and 59 women had newly diagnosed NIDDM, and 82 men and 188 women had previously diagnosed NIDDM. Participation rate was 71%. Main outcome measures were prevalence rates of CHD, stroke, and intermittent claudication. RESULTS--There was no difference in the prevalence of definite or possible MI verified at hospital between subjects with asymptomatic hyperglycemia and NGT (15.5 vs. 13.3% in men, 6.3 vs. 5.3% in women). Men with asymptomatic hyperglycemia had 1.5 x higher prevalence of angina pectoris (29.4 vs. 19.3%, P less than 0.05), major Q-QS changes (21.1 vs. 12.0%, P less than 0.05), ischemic ECG changes (59 vs. 45%, P less than 0.05), and silent MI on ECG (14.8 vs. 7.9%, P less than 0.05) compared to men with NGT. Women with asymptomatic hyperglycemia had more often ischemic ECG changes compared to women with NGT (48.3 vs. 39.7%, P less than 0.05). There was no difference (NS) in the prevalence of verified stroke (3.5 vs. 4.6% in men, 2.7 vs. 2.5% in women) or claudication (7.0 vs. 7.7% in men, 4.6 vs. 4.3% in women) between subjects with asymptomatic hyperglycemia and NGT. In multiple logistic regression analyses, the association between risk factors and MI or ischemic ECG changes in subjects with asymptomatic hyperglycemia was not consistent. CONCLUSION--Elderly subjects with asymptomatic hyperglycemia (particularly men) tended to have an increased prevalence of CHD. Thus, asymptomatic hyperglycemia in the elderly is not a benign phenomenon but is associated with cardiovascular morbidity.
Diabetes Care 1992 Aug
PMID:Asymptomatic hyperglycemia and atherosclerotic vascular disease in the elderly. 150 3

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.
 ...
PMID:Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome. 151 73

The prevalences of risk factors and angiopathy were studied in 260 diabetic patients, 100 females and 160 males, 35-54 years old, in Uppsala. The prevalence, in females and males separately, of hypertension (WHO-criteria) was 46-34%, of hypercholesterolaemia (greater than or equal to 6.7 mmol.l-1) 32-29%, and of obesity (relative BMI greater than or equal to 120%) 25-20%. Those smoking greater than 15 cigarettes/day were 11-20%. Mean HbA1 was 10.6-10.5%. The prevalence of angina pectoris was 11-6%, of possible infarction 4-6%, and of major ECG abnormalities 6-4%. Large vessel (cardiovascular) disease was independently related to HbA1 (strongly), hypertension, cholesterol, age and familial NIDDM. The prevalence of severe retinopathy (blindness, new vessels or large hemorrhage) was 0% with 7-13 years of diabetes duration, and 26% with greater than or equal to 14 years of duration. The prevalence of severe proteinuria was 4% with 7-13 years of diabetes duration, and 15% with greater than or equal to 14 years of duration. Small vessel (retinopathy and nephropathy) disease was independently related to diabetes duration (strongly), HbA1 and hypertension. The data were discussed related to data from the London, Berlin and Tokyo centres of the WHO Multinational Study of Vascular Disease in Diabetics, using the same study protocol in the present study.
 ...
PMID:Prevalences of risk factors and angiopathy in diabetic patients in Uppsala. 152 37

A review of the putative risk factors associated with the development of coronary heart disease in diabetes is presented. Emphasis is given to the effect of nephropathy (persistent proteinuria) and hypertension on cardiovascular mortality in IDDM. Risk factors associated with CHD in NIDDM are also reviewed. Finally, possible reasons to explain the increased incidence of CHD associated with proteinuria in IDDM patients, including lipoprotein abnormalities, increased fibrinogen levels, increased platelet adhesiveness, and altered hemostatic variables, are discussed.
Diabetes 1992 Oct
PMID:Risk factors for coronary heart disease in diabetes mellitus. 152 26

In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein pattern is antiatherogenic in individuals with IDDM who are treated and have optimal glycemic control. In contrast, NIDDM is associated with atherogenic changes of serum lipids and lipoproteins regardless of the mode of treatment. In people with both types of diabetes, the distribution of apoE phenotype seems to be similar to that in nondiabetic populations. IDDM patients with microalbuminuria show atherogenic changes of lipoproteins and have elevated levels of Lp(a), which is a risk factor of coronary artery disease. Whether glycemic control influences the concentration of Lp(a) is still an open question. An important issue is that the concentration of a lipoprotein can be normal without excluding compositional abnormalities that are potentially atherogenic. Such alterations are present in people with both IDDM and NIDDM. Consequently, it has been questioned whether the target values to start treatment should be lower in diabetic than in nondiabetic populations.
Diabetes 1992 Oct
PMID:Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus. 152 30

The usual choice of therapy in NIDDM diabetes, using oral anti-diabetic compounds, insulin or associated treatments, is based on the results of treatment evaluated empirically using glycemic profiles. As a contribution to the search for a method of choosing a treatment which is based on laboratory data and can restore metabolic equilibrium as quickly as possible using the most efficacious drug at an optimal dose, the paper reports a method of assessing the severity of diabetes according to mean daily glucose concentrations, the degree of instability in relation to the standard deviation, and proposes a sensitivity test to SU which indicates the choice of therapy, together with an insulin sensitivity test which is useful for evaluated the optimal dose. Sensitivity to SU evaluated using this method is not dependent on the degree of severity of diabetes. With regard to its practical use for prescribing treatment the test is highly predictive in positive cases since it is extremely sensitive, while its low specificity does not rule out its use in cases of resistance. The analysis of the results obtained after treatment which was not indicated by the sensitivity tests but based on personal experience and the comparison of the two methods shows that a high percentage of patients received inadequate therapy either due to the prescription of the wrong type of treatment or an incorrect dosage.
 ...
PMID:[Model of therapeutic programming in NIDDM diabetes]. 155 59

The goal of this study was to evaluate in 98 diabetic patients the serum levels of osteocalcin (OC) and their relationship with glycosylated hemoglobin levels and with the duration, calculated in years, of the disease. Patients were divided in 3 groups: 17 IDDM patients, 62 NIDDM patients treated with oral hypoglycaemic agents, and 19 NIDDM patients treated with insulin. Results were compared to 2 different control groups. In IDDM patients OC serum levels were significantly lower if compared either to control group and to NIDDM patients. The 2 groups of NIDDM patients showed significantly higher OC values than controls. No significant relationship resulted between OC levels, the duration of diabetes and the glycosylated hemoglobin values. The results of the study indicate a direct correlation between pancreatic function and osteoblastic activity: insulin lack is associated with reduced OC serum levels.
 ...
PMID:[Serum osteocalcin and diabetes mellitus. A study of 98 patients]. 155 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>