Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
 ...
PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Weight reduction in non-insulin dependent diabetes mellitus (NIDDM) patients improves metabolic control, reduces cardiovascular risk factors, has blood pressure lowering effects and improves the well-being of the patient. This paper describes the role of very low calorie diets (VLCD), exercise, beta-adrenergic drugs and serotoninergic agents in the treatment of overweight in NIDDM. VLCD reduce body weight and improve glucose metabolism. Physical exercise programmes in addition to dietary restriction substantially contribute to weight loss and metabolic control in NIDDM. New specific beta-adrenergic agents, exhibiting virtually no beta 1 or beta 2 activity, increase energy expenditure and weight loss probably by enhancement of the basal metabolic rate. The target tissue in humans of this beta-adrenergic effect is as yet unknown. These drugs seem to enhance weight loss when used in combination with (very) low calorie diets compared to dietary restriction alone. Serotoninergic drugs reduce body weight by decreasing appetite, in particular for carbohydrates. Furthermore these drugs seem to improve insulin receptor sensitivity.
 ...
PMID:Very low calorie diets and recently developed anti-obesity drugs for treating overweight in non-insulin dependent diabetics. 136 97

The relationship between obesity and type II diabetes mellitus is well established and a majority of type II diabetic individuals are classified as obese. The pathogenesis of type II diabetes mellitus is not fully understood; however, multiple organ systems are involved, including abnormalities of insulin secretion, peripheral insulin resistance and hepatic insulin resistance. The goal of the treatment for the obese diabetic is to normalise these alterations and achieve normoglycaemia. Traditionally, the initial therapy, aiming to accomplish weight reduction, is diet and exercise. In obese type II diabetic patients, the whole body insulin-dose response curve is markedly depressed. A single exercise session improves and partially normalises both insulin responsiveness and sensitivity for glucose utilisation. Furthermore, a single bout of physical activity often results in decreased plasma glucose levels, which persists into the postoperative period. Type II diabetes patients participating in regular exercise programmes can potentially improve their metabolic control. An improved glucose control in both lean and obese type II diabetic patients under the age of 55 years has been demonstrated by improved HbA1C levels and glucose tolerance tests following physical training programmes. The effect of regular exercise on the metabolic control in these younger patients does not appear to be correlated with weight reduction. For most type II diabetic men over 55 years of age, physical training is not a feasible form of therapy because of other interfering diseases which may complicate or severely hinder all physical training apart from very low intensity exercise programmes. Lean, older, type II diabetic patients who have been able to exercise for 10 weeks or up to 2 years demonstrate no change in HbA1C levels, glucose tolerance or bodyweight. Thus, there is a clear difference in metabolic response to regular exercise between younger and older type II diabetic patients. The younger patient appears to be more inclined to respond to physical training with improvements in the metabolic control. The reason for this apparent difference is not clear, but possible explanations may include differences in training intensity, the presence or degree of complicating diseases, pretraining level of metabolic control or bodyweight. Type II diabetics are predisposed to cardiovascular disease and are characterised by hyperlipidaemia. In obese type II diabetic individuals, physical training improves the blood lipid profile as measured by decreased levels of triglycerides and total cholesterol. In young, overweight diabetics, improved lipid profiles can be achieved despite no change in bodyweight, while no apparent effects are reported for lean patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Exercise training in obese diabetic patients. Special considerations. 143 93

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. 173 2

Insulin resistance appears as the pathophysiological basis of metabolic syndrome and NIDDM. In type 2 diabetics additionally we observe a delayed and prolonged postprandial insulin response. These both processes represent a pathophysiological and pathogenetic unity of disturbances. The prevention and therapy of insulin resistance, metabolic syndrome and type 2-diabetes with diet involves 3 main issues: reduction of energy uptake and of body weight in obese; Composition of meals concerning the principles of fat reduced lactovegetabile nutrition; guaranteeing of longer postabsorptive phases (between meals), to avoid a permanent postprandial hyperinsulinemia and development of insulin resistance. Anti-insulin resistance diet is therefore a carbohydrate enriched, fat-reduced (lactovegetabile) nutrition with not too frequent meals (longer meal-free phases) and mainly reduced energy intake in overweight.
 ...
PMID:[Treatment of type 2 (non-insulin dependent) diabetes and the metabolic syndrome with diet]. 177 27

The efficacy and safety of gliclazide (Diamicron) were studied in 29 NIDDM patients (19 men and 10 women aged 25-68 years) who failed to improve with diet or with diet plus a sulfonylurea. All patients were overweight and had fasting blood glucose levels consistently above 150 mg/dl (8.24 mmol/l). After withdrawal of oral hypoglycemics where applicable, they received 40 mg Diamicron three times daily with meals. The dose was increased by 40-80 mg/day until optimum control was obtained or up to a maximum of 320 mg/day. Treatment lasted for 12 months. At the end of this period the mean fasting blood glucose level had fallen by 35% from 238 to 154 mg/dl and the mean 2-h postprandial blood glucose level had fallen by 28% from 237.7 to 195 mg/dl. The mean glycosylated hemoglobin level also fell by 30% from 10.10 to 7.02%, i.e. within the normal range. In addition, there was a 19% fall in triglyceride and a 10% fall in cholesterol levels, with no change in body weight. No changes were observed for serum insulin, C-peptide and glucagon levels, thyroid function tests, blood counts, liver and kidney function tests, uric acid, electrolytes, blood pressure or heart rate. No clinical or ECG abnormalities were observed in patients with or without cardiovascular disease. There were two presumptive hypoglycemic reactions, but these did not require treatment. Adverse effects were reported by 22 patients, including dizziness and light-headedness, diarrhea, nausea, palpitations and pruritus, but none required modification of Diamicron therapy. The results therefore show that Diamicron is safe, effective and well tolerated in suitably selected NIDDM patients.
 ...
PMID:Evaluation of the efficacy and safety of Diamicron in non-insulin-dependent diabetic patients. 179 70

The Authors studied the behaviour of some prothrombotic (fibrinogen, factor VII, antithrombin III and tissue plasminogen activator) and prethrombotic (beta thromboglobulin, D-dimer) markers in a group of obese subjects in relation to various physiopathological parameters. The series consist of 93 obese subjects (29 m, 64 f, mean age 55 +/- 6 yrs, BMI 33 +/- 1), of whom 62 suffering from type 2 diabetes in good metabolic control obtained by oral hypoglycemic (42 cases) or insulin (20 cases) treatment. For each subject the Authors determined the plasmatic levels of glucose, total cholesterol, triglycerides (enzymatic method, Boehringer kits), fibrinogen (coagulometric method, Organon kit), factor VII (chromogenic method, IL kit), antithrombin III (chromogenic method, IL kit), tissue plasminogen, beta thromboglobulin and D-dimer (ELISA method, Boehringer kits). The results were examined in relation to sex, age, overweight degree, waist/thigh ratio, total cholesterol, triglycerides and, for diabetics, to the therapeutical treatment. The fibrinogen plasma levels proved statistically (0.05) increased proportionally to the overweight degree (BMI over 35), cholesterol levels (over 250 mg%) and age (51-65 yrs); factor VII showed a significant increase (0.05) related to the cholesterol levels, the overweight degree and, surprisingly, to female sex; as regards antithrombin III, its sharp reduction was related with ageing and with the "gynoid type" waist/thigh ratio; tissue plasminogen activator showed a statistically significant reduction (0.05) in the group with older age (over 65 yrs); the beta thromboglobulin levels were obviously increased (0.05) in the hypercholesterolemic and hypertriglyceridemic subjects (over 250 mg%), the D-dimer values increased proportionally with age (0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Prothrombotic and prethrombotic markers in obese diabetic and non-diabetic subjects]. 183 Mar 76

Twenty-five newly presenting, untreated, white, non-insulin-dependent diabetic (NIDDM) subjects were studied within 72 hours of diagnosis. They were allocated to three groups according to their body mass index [BMI] (lean BMI less than 25.0, n = 9; overweight BMI 25.0 to 30.0, n = 6; obese BMI greater than .30.0 kg/m2, n = 10). All three groups exhibited equivalent hyperglycemia. Eleven normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, before and during a 240-minute insulin infusion (100 mU/kg/h). Fractional GS activity did not increase in the lean (change, -0.9 +/- 3.3%), the overweight (-1.9 +/- 2.7%), or the obese (+2.2 +/- 1.6%) NIDDM subjects during the insulin infusion and was markedly decreased compared with the control subjects (change, +14.6 +/- 2.4%, all P less than .001). Glucose requirement was also significantly decreased in all three NIDDM groups (103 +/- 23 v 81 +/- 14 v 53 +/- 14 mg/m2/min, respectively) compared with the control subjects (319 +/- 18 mg/m2/min, all P less than .001). There was a significant negative correlation with BMI (r = -.51, P less than .01), but the difference in glucose requirement between the lean and obese NIDDM groups was not significant. Muscle GS activity at the end of the euglycemic clamp correlated with glucose requirement (r = .53, P less than .001), and a similar correlation was observed between the insulin-induced change in muscle GS activity from basal and glucose requirement (r = .47, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impaired activation of skeletal muscle glycogen synthase in non-insulin-dependent diabetes mellitus is unrelated to the degree of obesity. 190 Mar 43

The attempt has been made to identity the lowest dose of glipizide, a second generation sulphonylurea, capable of improving glucose tolerance in overweight and obese subjects with various degrees of glucose tolerance. Thirty one obese subjects, 12 with non insulin dependent diabetes mellitus (NIDDM), 9 with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT) each underwent four OGTTS (75 g), at 1 week intervals, after administration in random order of placebo or glipizide 0.5, 1.0 or 2.5 mg 30 min before glucose. Glucose tolerance in all groups was progressively improved by the increasing doses of glipizide and was normalized by 1.0 mg glipizide in impaired glucose tolerance (IGT) and by 2.5 mg glipizide in NIDDM. Insulin release was not significantly affected by glipizide in the three groups of subjects. The data indicate that it is possible, at least in acute experiments, to improve glucose tolerance in overweight and obese subjects with IGT, with NGT and with NIDDM, with doses of glipizide that do not affect insulin release.
 ...
PMID:Acute effect of glipizide on glucose tolerance in obesity and diabetes mellitus (NIDDM). 206 May 41

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.
 ...
PMID:Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM. 207 83


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