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

In 43 patients with non-insulin dependent diabetes mellitus (NIDDM) associated with hypercholesterolemia, the effect of pravastatin, a potent HMG CoA-reductase inhibitor, on serum lipids, apolipoproteins and lipoprotein (a) was examined. After 1 to 3 months administration of 10 mg per day of pravastatin, the serum levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, while the serum level of high density lipoprotein cholesterol (HDL-C) was significantly increased in patients with NIDDM. The levels of apolipoproteins B (apo B) and E were significantly decreased, while apolipoprotein AI (apo A-I) was not changed by the administration of pravastatin. The atherogenic indices (LDL-C/HDL-C and apo B/apo A-I) were significantly decreased by the administration of this drug. The serum lipoprotein (a), which was increased in the diabetic patients, was not affected by the pravastatin treatment. Plasma glucose and hemoglobin A1c levels were not affected by the treatment. We concluded that pravastatin is a potentially useful agent in the treatment of hypercholesterolemia in patients with NIDDM.
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PMID:Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus. 153 40

To investigate the possible role of islet amyloid polypeptide (IAPP) in the development of type 2 diabetes mellitus, we examined the IAPP content and secretion in pancreatic islets isolated from ventromedial hypothalamic (VMH)-lesioned rats and genetically obese Zucker rats, using a specific radioimmunoassay for IAPP. Obesity and hyperinsulinemia were observed in rats 21 days after VMH lesioning. IAPP content was increased in the islets of VMH-lesioned rats compared with findings in the sham-operated controls (100.9 +/- 6.6 vs 72.8 +/- 3.85 fmol/islet; P less than 0.01). Isolated islets of VMH-lesioned rats secreted larger amounts of IAPP in the presence of 2.8 and 16.7 mM glucose (2.99 +/- 0.98 and 11.2 +/- 0.29 fmol islet-1 3 h-1) than was noted in sham-operated rats (ND and 6.65 +/- 0.78 fmol islet-1 3 h-1). In the obese Zucker rats, aged 14 weeks, IAPP concentrations in the islets were elevated compared with lean rats (133.3 +/- 10.6 vs 84.4 +/- 8.5 fmol/islet; P less than 0.01). The isolated islets secreted larger amounts of IAPP in response to 2.8 and 16.7 mM glucose (2.83 +/- 0.88 and 15.81 +/- 1.35 fmol islet-1 3 h-1) than did those from lean control rats (0.36 +/- 0.19 and 12.49 +/- 1.20 fmol islet-1 3 h-1). These results strongly suggest that overproduction and hypersecretion of IAPP occur in animals with obesity and hyperinsulinemia.
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PMID:Hypersecretion of IAPP from the islets of VMH-lesioned rats and obese Zucker rats. 154 Dec 31

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased very-low-density lipoprotein (VLDL) and triglyceride concentrations as abnormalities of low-density lipoprotein (LDL) composition. Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects, we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM (n = 19), who until now were not treated by drugs but only by diet. The study was started with a placebo-run-in-period for four weeks (phase I, 6 g rape seed oil capsules/d), followed by a verum period for twelve weeks (phase II, 6 g fish oil concentrate capsules/d), and a wash-out-period for four weeks (phase III, 6 g rape seed oil capsules/d). The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid. The lipoproteins, apolipoproteins, blood glucose, and insulin level (fasting and after load test) were checked at the beginning and at the end of each phase. In comparison to the placebo rape seed oil supplementation, the fish oil diet effected a decrease of serum triglycerides by 29%. LDL-cholesterol increased by 9%, HDL-cholesterol by 9% (especially HDL2-cholesterol), and apolipoprotein B by 4%. Apolipoprotein A-I was reduced by 9%. The fasting blood glucose and the glucose load test as the insulin level (fasting and after load test) showed no significant changes at the end of the verum period in comparison to the run-in-phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of fish oil concentrate on the lipoprotein profile of patients with type II diabetes mellitus]. 154 65

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM.
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PMID:Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. 154 70

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.
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PMID:[Model of therapeutic programming in NIDDM diabetes]. 155 59

We studied the 1-year response and predictors of the response to combination therapy with evening insulin and oral agents in NIDDM patients with a secondary failure. Injection of intermediate-acting (Monotard HM) or long-acting (Ultratard HM) insulin was added to previous oral therapy in 17 diabetics (of mean age (+/- SD) 54 +/- 2 years, BMI 27.6 +/- 0.5 kg m-2). The initial insulin dose was in the range 10-16 U, and the mean dose was 23 +/- 2 U d-1 at 12 months. During the year, combination therapy reduced the mean fasting blood glucose concentration (12.7 +/- 0.6 vs. 8.4 +/- 0.7 mmol l-1, P less than 0.001) and HbA1 (10.7 +/- 0.3 vs. 9.8 +/- 0.4%, P less than 0.01). Body weight increased by 4.4 +/- 0.7 kg (P less than 0.001). The serum cholesterol concentration decreased by 14% (P less than 0.01), but serum triglyceride and HDL-cholesterol levels remained unchanged. Elevation of serum triglycerides and plasma free fatty acids (FFAs) at baseline predicted a poor long-term outcome to this mode of therapy. In conclusion, the addition of evening injections of insulin to oral therapy improves glycaemic control in poorly controlled NIDDM patients. However, initial hypertriglyceridaemia predicts a poor long-term outcome to evening insulin supplementation.
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PMID:One-year response to evening insulin therapy in non-insulin-dependent diabetes. 155 22

Non-insulin-dependent diabetes mellitus is characterized by abnormal beta-cell function. The characteristic secretory defect is a selective loss of glucose-induced insulin secretion. Substantial data have been generated in animal models to support the concept that chronic hyperglycemia causes the loss of glucorecognition (the so-called glucose toxicity hypothesis). This review summarizes the data supporting the concept of hyperglycemia-induced beta-cell dysfunction and then focuses on the ideas for the mechanism of the glucose unresponsiveness. The lack of access to islet tissue in humans means that these studies have all been conducted in animal models. Another major stumbling block continues to be the lack of in vitro systems that faithfully reproduce the secretory abnormalities that occur in vivo. Despite these limitations, many hypotheses are being investigated that span most of the major intracellular steps for glucose-induced insulin secretion, including abnormalities in glucose transport, storage, metabolism/oxidation, and the second messengers. No single hypothesis stands out as being able to explain all of the characteristics of the secretory abnormalities. In the last few years major advances have occurred in our knowledge about the events that normally cause glucose-induced insulin secretion. Similarly, biochemical and molecular tools have become available to probe the different steps. As better in vitro models of the selective glucose unresponsiveness become available, rapid progress can be expected in unraveling the biochemical basis for the loss of glucose responsiveness in diabetic rat models. The long-term hope is that this information will lead to innovative new strategies for the therapy of non-insulin-dependent diabetes mellitus.
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PMID:Beta-cell dysfunction induced by chronic hyperglycemia. Current ideas on mechanism of impaired glucose-induced insulin secretion. 155 11

The European NIDDM Policy Group classifies both fasting and post-prandial blood glucose concentrations into 'good', 'acceptable', and 'poor' categories. The aim of the present study was to evaluate whether a 'good' fasting blood glucose concentration in Type 2 diabetic patients on diet or diet + oral hypoglycaemic agents is able to predict 'good' blood glucose values throughout the day, and therefore to discover whether or not it is necessary to perform blood glucose profiles in Type 2 diabetic patients when their fasting value is 'good'. Capillary blood glucose profiles (n = 417) were measured in 287 Type 2 diabetic patients, on diet alone (279 profiles), or on diet + tablets (138 profiles). We observed that 66% of profiles on diet and 44% of profiles on diet + tablets had only 'good' blood glucose concentrations (p less than 0.001). Eleven percent of profiles on diet and 30% of profiles on diet + tablets included 'poor' blood glucose concentrations (p less than 0.001). Despite matched fasting blood glucose concentrations (diet 5.69 +/- 0.04 (+/- SE) vs tablets 5.75 +/- 0.05 mmol l-1), levels were higher in the diet + tablet treated patients at all later time-points (p less than 0.01-0.001). HbA1c was significantly higher in tablet-treated patients than in patients on diet alone (6.6 +/- 0.1 vs 5.9 +/- 0.1%, p less than 0.001), and correlated with the mean blood glucose concentration (r = 0.43, p less than 0.001) but not with the fasting glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of the predictive power for overall blood glucose control of a 'good' fasting level in type 2 diabetic patients on diet alone or with oral agents. 156 47

It is well known that intensive insulin treatment of non-insulin-dependent diabetics (NIDDM) suppresses endogenous insulin secretion and thereafter improves it. To determine whether 'peripheral normo-insulinemia' or 'normoglycemia' established by the treatment is responsible for this suppression, the following five experiments were conducted on 15 well-controlled non-obese NIDDM patients. Experiment 1: a 100 g oral glucose load (OGL) was performed and blood glucose was monitored by an artificial endocrine pancreas (AP). Experiment 2: a 100 g OGL was done and blood glucose was normalized by AP-controlled insulin infusion. Experiments 3 and 4: a 100 g OGL was conducted while 'hyperglycemia' seen in experiment 1 was mimicked by AP-controlled glucose infusion with pre-programmed insulin infusion at the same rates as those in experiment 2 ('normoinsulinemia') or at rates 1.5 times higher than those in experiment 2 ('relative hyperinsulinemia'), respectively. Experiment 5: a 40 g OGL was conducted while AP-controlled insulin and glucose infusions were administered to make the plasma insulin level lower than in experiment 2 ('hypoinsulinemia') and to mimic the normoglycemic profile observed in experiment 2, respectively. In experiments 3 and 4, neither 'normoinsulinemia' nor 'relative hyperinsulinemia' suppressed the increase in plasma C-peptide after a 100 g OGL. In experiment 5, where the plasma insulin level showed a significantly (P less than 0.05) lower level than in experiment 2 and glycemia was normalized, C-peptide did not show a significant rise after OGL. These results indicate that 'normoglycemia' rather than 'normoinsulinemia' attained during exogenous insulin therapy, is responsible for suppressing endogenous insulin secretion against orally administered glucose.
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PMID:Normoglycemia per se but not normoinsulinemia is responsible for suppressing endogenous insulin secretion after oral glucose load in NIDDM. 156 27

We investigated how different plasma glucose concentrations could significantly modify the C-peptide response to glucagon. Twenty poorly-controlled (HbA1c 10.2 +/- 1.5%) non insulin-dependent (NIDDM) subjects (body mass index 27 +/- 1.8), 2 treated with diet alone and 18 with oral hypoglycemic agents were studied. The first day glucagon (1 mg iv) was injected, patients being fasting and untreated. Mean plasma glucose levels were 11.4 +/- 1.2 mM. On a second non consecutive day, after an overnight fast, the same patients were connected to a closed-loop insulin infusion system (Betalike, Genoa), their blood glucose concentrations were stabilized within a normoglycemic range (5-5.5 mM) for 2 h and insulin infusion was stopped. The glucagon test was repeated 30 min later. Blood samples were taken 0, 6, 10, 20 min after glucagon injection. In the second test, basal, and 6, 10 and 20 min post-glucagon glucose levels were significantly lower (p less than 0.001); similarly C-peptide concentrations were significantly reduced both in basal conditions (0.55 +/- 0.04 vs 0.37 +/- 0.04 nM; p less than 0.001) and 6 (0.92 +/- 0.06 vs 0.6 +/- 0.06; p less than 0.001), 10 (0.79 +/- 0.06 vs 0.56 +/- 0.06; p less than 0.001) and 20 min (0.64 +/- 0.05 vs 0.44 +/- 0.04; p less than 0.001) after stimulation. The C-peptide secretion area showed the same trend (49.5 +/- 4.8 vs 32.1 +/- 5.8; p less than 0.001). In conclusion, our data confirms that blood glucose levels modulate the pancreatic insulin secretion; glycemic normalization significantly reduced both basal and post-glucagon C-peptide release.
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PMID:The effect of various blood glucose levels on post-glucagon C-peptide secretion in type 2 (non insulin-dependent) diabetes. 156 91


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