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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-acting effect of a 10-min pulse infusion of the beta 2-adrenergic agonist fenoterol on oral glucose tolerance tests in controls and in normotensive patients with type 2 diabetes mellitus on diet was compared. During an oral glucose load starting 2 h after fenoterol control persons showed hyperglycemia (area: 25,950 +/- 467 vs. 22,650 +/- 410, P less than 0.01), hyperinsulinemia (area: 13,980 +/- 1050 vs. 8160 +/- 405, P less than 0.02) and a pronounced fall of serum potassium (area: 775 +/- 26 vs. 748 +/- 25, P less than 0.02). The patient group showed no late response to fenoterol: plasma glucose (area: 51,000 +/- 382 vs. 51,300 +/- 413, n.s.), serum insulin (area: 7215 +/- 233 vs. 8280 +/- 410, n.s.), serum potassium (area: 748 +/- 26 vs. 750 +/- 24, n.s.). The data show that there is a defect of the beta 2-adrenergic long-acting effect on glucose metabolism and on insulin release in type 2 diabetes mellitus.
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PMID:Lack of beta 2-adrenoceptor induced long-acting effect on glucose tolerance in type 2 diabetic patients. 166 46

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
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PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia secondary to increased hepatic glucose output and impaired extrahepatic insulin sensitivity. Many NIDDM patients also have raised serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, which may require drug therapy, as well as increased plasma nonesterified fatty acid concentrations. Some hypolipidemic agents such as bezafibrate lower fatty acid levels as well as LDL cholesterol and triglycerides. It has been suggested that raised fatty acid levels may be responsible in part for the increased hepatic glucose output and insulin insensitivity of NIDDM. Several groups have therefore sought to examine the effects of fibrates on glycemic control in NIDDM. In our own studies, we used bezafibrate (200 mg t.i.d.) in a double-blind, placebo-controlled design for 3 months. Fasting blood glucose, serum insulin, C-peptide, plasma nonesterified fatty acids, blood lactate and alanine, serum triglycerides, and LDL cholesterol were all lowered. HbA1 showed no significant change. Meal hormone and metabolite profiles were all improved although this reflected mainly the lower premeal values. The results of our and other studies are sufficiently encouraging to suggest that bezafibrate could provide alternative first-line drug therapy in hyperlipidemic NIDDM patients when diet alone has failed.
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PMID:Effect of bezafibrate on metabolic profiles in non-insulin-dependent diabetes mellitus. 171 Jul 41

Nearly 50% of individuals with type II diabetes mellitus are over the age of 65 years. There are numerous reasons to maintain blood glucose levels below 11.1 nmol/L (200 mg/dl) in older persons, and there are a number of changes often seen with advancing age that persons, and there are a number of changes often seen with advancing age that may interfere with the management of diabetes mellitus, e.g. hypodipsia, anorexia, visual disturbance, altered renal and hepatic function, depression, impaired basoreceptor response and multiple medications. Hyperglycaemia appears to produce cognitive impairment which may lead to poor compliance. It is often difficult to manipulate diet in older people, and in fact dietary changes can lead to severe protein energy malnutrition. High maximum voluntary oxygen intake has been correlated with increased glucose disposal, but there is little evidence that physical exercise can improve diabetic control in the elderly. Oral sulphonylurea hypoglycaemic agents are extremely useful in the treatment of diabetes in these patients, but it should be remembered that they are more liable to develop hypoglycaemia than are younger diabetics. The role of metformin in the management of older diabetic patients is poorly studied. Many older persons can cope well with insulin therapy, but those with visual disturbances often make errors when drawing up insulin and require special attention. Combination therapy of insulin with oral hypoglycaemic agents is not recommended in this group of patients, and serum fructosamine is preferred to glycated haemoglobin to monitor control. Successful management of elderly diabetic patients thus requires an interdisciplinary team approach.
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PMID:The management of diabetes mellitus in older individuals. 171 59

To evaluate whether intranasal insulin might be useful as a meal-adjunct in the treatment of NIDDM we compared plasma glucose and insulin responses to a mixed breakfast (9 kcal/kg, 50% carbohydrate) following either intranasal insulin (INI) or placebo in eleven patients with NIDDM. Five patients treated with subcutaneous insulin and in good to moderate glycemic control and six patients who were 'failing' on oral agents and in poor glycemic control were studied. In the patients usually on sc insulin, INI inhibited postprandial hyperglycemia. Lower doses (1 U/kg vs 1.5 U/kg b.w.) were needed to accomplish this in 2 patients with low fasting glucose (less than or equal to 7.8 mmol/l) than in three patients with higher fasting glucose (10.5 +/- 0.5 mmol/l). In the patients on oral agents who had marked fasting hyperglycemia (14.8 +/- 0.8 mmol/l) an only transient reduction (for 90 to 120 min) of postprandial hyperglycemia was achieved when INI (1 U/kg) was given in addition to po glyburide (10 mg) prior to the meal. Following placebo in the group previously treated with sc insulin, plasma free insulin levels increased maximally by 23 mU/l, 75 min after the meal. The group on oral agents had a comparable but later peak increment (at 180 min) indicative of an even greater impairment of endogenous insulin secretion in response to hyperglycemia. Following INI, the peak increment in plasma insulin occurred earlier (30 min after the meal) and was greater in all patients (55 +/- 18, 139 +/- 68, 86 +/- 24 mU/l respectively for the prior sc insulin therapy group at doses of 1.0 and 1.5 U/kg and for the oral agent group at 1.0 U/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Could intranasal insulin be useful in the treatment of non-insulin-dependent diabetes mellitus? 177 16

There are two approaches to identify diabetes-susceptibility genes. One approach is to isolate and characterize genes expressed in the beta-cell and in insulin target tissues whose mutation or altered expression may contribute to the development of diabetes mellitus. Another approach is to clone a diabetes-susceptibility gene by a reverse genetic strategy. The first step for this strategy is to identify a DNA polymorphism that is linked to the disease locus. Using the strategy of the first approach, several candidate genes were examined. Among these genes, the mutation of insulin genes and insulin receptor genes was found in the patient with diabetes. By cDNA cloning or PCR-direct sequencing methods, we identified several mutations in the insulin receptor genes of four insulin-resistant diabetic patients. At least two mutants of insulin receptor genes were expressed in Chinese hamster ovary cells and these mutated receptors showed impaired ability to transduce insulin action in these cultured cells. The expression of these mutant genes in animals such as transgenic mice will be indispensable to establish the relationship between the gene mutation and the abnormality found in the patient. Using the strategy of the second approach, Bell et al. recently reported that the gene responsible for MODY (maturity-onset diabetes of the young) is tightly linked to the adenosine deaminase gene on chromosome 20q. However, this strategy will not be applicable for identification of diabetes-susceptibility genes of NIDDM, since this disorder is likely to be genetically heterogenous, with mutations in several different genes able to cause hyperglycemia, and this heterogeneity could confound the linkage analysis.
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PMID:[Diabetes mellitus and molecular biology]. 177 65

Release of immature secretory granules rich in incompletely processed proinsulin has been proposed to explain the relative hyperproinsulinemia in type 2 diabetic and insulinoma patients because of a constant secretory drive resulting from hyperglycemia and autonomous secretion, respectively. To test this hypothesis, insulin secretion was stimulated by a combination of hyperglycemia (11 mmol/L clamp), intravenous (i.v.) tolbutamide (1 g), and i.v. glucagon (initial bolus 10 micrograms/kg body weight, maintenance infusion 2 micrograms/kg body weight per hour) for 3 h. Circulating IR-insulin and IR-C-peptide concentrations increased 89-fold and 14-fold over basal values, respectively, but IR-proinsulin concentrations increased only ninefold over basal values. Estimation of the amount of insulin secreted (based on deconvolution analysis of plasma C-peptide values) showed that approximately 76 +/- 21 U were secreted during the stimulation period. This amount is a significant proportion of pancreatic insulin content in normal humans. In molar terms, IR-proinsulin (integrated incremental response multiplied by metabolic clearance rate of proinsulin) relative to IR-C-peptide (= insulin) secretion (deconvolution analysis) was estimated to be equal or even lower than the known proportion in islets (0.22 +/- 0.05%). Thus, using a near-maximal stimulation of insulin secretion maintained long enough to cause release of amounts of insulin approaching the estimated pancreatic content, no preferential release of proinsulin was observed in normal humans. Therefore, the hyperproinsulinemia of type 2 diabetes and in insulinoma patients may be caused by additional defects in the proinsulin to insulin conversion process.
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PMID:Prolonged maximal stimulation of insulin secretion in healthy subjects does not provoke preferential release of proinsulin. 178 Mar 24

The hemovascular abnormalities encountered in diabetes include platelet alterations, shifts in prostaglandin metabolism and disorders of fibrinolysis. Diabetes is thus associated with increased platelet adhesiveness, increased platelet aggregation with hypersensitivity to proaggregants, increased plasma levels of beta-thromboglobulin and platelet factor 4 as an expression of platelet hyperactivity, increased levels of thromboxane A2 (TXA2) and prostacyclin (PGI2), and reduced levels of tissue plasminogen activator (t-PA). It is not clear which, if any, of these abnormalities are generated by chronic hyperglycemia and can be corrected by adequate glycemic control. Studies with gliclazide have demonstrated that it exerts hemovascular effects which can be valuable to patients. Thus, treatment with gliclazide leads to a decrease in platelet adhesiveness and aggregability. This treatment also reduces thromboxane levels and increases TPA levels. The mechanisms of action of gliclazide are not fully known but it has been demonstrated that its antiplatelet action is independent of its hypoglycemic activity and is not accompanied by clinical abnormalities of blood clotting. The mechanism of direct action on platelet activity may be mediated by inhibition of activated glycogen synthetase, activation of adenylate cyclase, modulation of arachidonic acid release from platelet membranes, stimulation of PGI2 production, and inhibition of the proaggregant action of TXA2. Thus, gliclazide not only has a hypoglycemic action but also improves hemovascular parameters in type 2 diabetes when used at normal therapeutic doses.
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PMID:Hemobiological activity of gliclazide in diabetes mellitus. 179 71

One of the earliest histopathological signs of diabetic retinopathy is a selective loss of intramural pericytes from retinal capillaries. In the present study, the retinal vessels of rats with streptozotocin-induced diabetes (STZ Wistar) and rats with genetically-induced insulin dependent diabetes mellitus (BB Wistar) and non-insulin dependent diabetes mellitus (SHR/N-corpulent) were examined after 6 to 8 months duration for diabetes-related retinal microangiopathies. The SHR/N-corpulent (cp) rats were fed a 54% sucrose diet, whereas the STZ Wistar and BB Wistar rats were fed laboratory chow for 32 to 36 weeks. In all the diabetic rats, the retinal capillaries in enzyme-digested flat mounts exhibited an increase in periodic-acid-Schiff (PAS) staining and loss of pericytes compared to their respective euglycemic controls. Pericyte "ghosts", like those defined in human diabetes as intramural pockets lacking normal cell contents, were documented by high resolution micrographs in all the diabetic rats. Endothelial cell proliferation, capillary dilation, and varicose loop formation were noted in some of the diabetic rats. Hence, similar capillary lesions were found in very different groups of diabetic rats. The findings suggest that a chronic high tissue concentration of glucose is the underlying factor which triggers pathogenesis in the pericyte. Hyperglycemia-induced activation of endogenous aldose reductase of the polyol pathway is probably the initial insult, but other factors such as advanced glycosylation products may affect the final outcome.
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PMID:Degenerated intramural pericytes ('ghost cells') in the retinal capillaries of diabetic rats. 182 96

Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of morbidity and mortality worldwide, with a prevalence of 3-7% in most Western countries. Decreased insulin secretion and diminished tissue insulin sensitivity are both implicated in the pathogenesis of the disease; both may be exacerbated by persistent hyperglycemia and improved by normalization of blood sugar levels. Measures to control hyperglycemia, hypertension, and hyperlipidemia are important in the management of NIDDM and prevention of its long-term complications. The effects of dietary modification, exercise, and antihypertensive and antiplatelet therapy, as well as of pharmacologic control of blood sugar, on the vascular and renal complications of NIDDM have been investigated. Gliclazide is a second-generation sulfonylurea drug whose efficacy in the treatment of NIDDM, alone or in combination with insulin, has been widely demonstrated. Studies of the use of gliclazide, reported at recent symposia, are summarized in this review.
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PMID:Current status of non-insulin-dependent diabetes mellitus (type II): management with gliclazide. 187 2


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