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)

Nateglinide is a new, fast-onset, short-acting hypoglycemic agent, which increases early phase insulin secretion and the total amount of insulin secreted. However, it is not clear which of these effects contribute more to the decrease in postprandial plasma glucose (PG). To further clarify the pharmacologic actions of nateglinide, we investigated the changes in PG and insulin levels during meal tolerance tests with and without nateglinide. Subjects were 10 newly diagnosed and untreated inpatients with type 2 diabetes. After diet and exercise therapy for 1 week, nateglinide at 270 mg divided 3 times a day, was started. Meal tolerance tests were performed before (baseline) and after a single nateglinide administration (day 1), after 7 days of repeated administration (day 7), and after cessation of nateglinide on day 8. Mean fasting PG was 146 +/- 6 mg/dl (mean +/- SEM) at baseline and 130 +/- 6 mg/dL on day 7 (P =.0004). The 2-hour postprandial PG level was 226 +/- 10 mg/dL at baseline, 145 +/- 11 mg/dL on day 1 (P =.0008), and 190 +/- 15 mg/dL on day 8 (P =.08, baseline; P =.01, day 7). The mean fasting insulin level was 5.4 +/- 1.0 microU/mL at baseline and did not change significantly during the study. The 30-minute postprandial insulin level was 14.4 +/- 1.9 microU/mL at baseline, 39.5 +/- 4.5 microU/mL on day 1 (P =.0004), and 23.6 +/- 3.6 microU/mL on day 8 (P =.045, baseline; P =.010, day 7). The total insulin amount, in terms of area under the curve (AUC. IRI), was 3.99 +/- 0.7 x 10(3) microU/mL. min at baseline, 5.47 +/- 0.8 microU/mL. min on day 1 (P =.029), and 6.01 +/- 1.9 microU/mL. min on day 8 (P =.047 v baseline). The early phase of insulin secretion, based on the ratio of delta IRI to delta PG from fasting to 30 minutes after a meal was 0.15 +/- 0.13 at baseline, 1.44 +/- 0.26 on day 1 (P =.0009) and 0.26 +/- 0.06 on day 8 (P =.05 v day 1). After cessation of nateglinide, the postprandial PG level increased immediately. Although early phase insulin secretion returned nearly to the baseline level, total insulin secretion remained at a high level. These results suggested that early phase insulin secretion contributes more than total insulin secretion to the improvement of postprandial hyperglycemia in type 2 diabetes.
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PMID:Improvement of glucose tolerance by nateglinide occurs through enhancement of early phase insulin secretion. 1178 67

Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.
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PMID:Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus. 1197 12

This study was initiated to see if plasma asymmetric dimethylarginine (ADMA) concentrations decreased in hyperglycemic patients with type 2 diabetes following metformin treatment, either as monotherapy or following its addition to sulfonylurea-treated patients. Fasting plasma glucose, dimethylarginine, and L-arginine concentrations were measured before and 3 months after the administration of a maximally effective dose of metformin to 31 patients with type 2 diabetes in poor glycemic control (fasting plasma concentrations > 9.7 mmol/L), while being treated with either diet (n = 16) or a maximal amount of a sulfonylurea compound (n = 15). Fasting plasma glucose concentration (mean +/- SEM) decreased to a similar degree (P <.01) in patients treated with either metformin alone (12.4 +/- 0.5 to 9.5 +/- 0.5 mmol/L) or when it was added to a sulfonylurea compound (14.1 +/- 0.5 to 10.6 +/- 0.9 mmol/L). The improvement in glycemic control was associated with similar decreases (P <.01) in ADMA concentrations in metformin (1.65 +/- 0.21 to 1.18 +/- 0.13 micromol/L) and sulfonylurea + metformin-treated patients (1.75 +/- 0.13 to 1.19 +/- 0.08 micromol/L). Plasma L-arginine concentrations were similar in the 2 groups at baseline and did not change in response to metformin. Thus, metformin treatment was associated with a favorable increase in the plasma L-arginine/ADMA ratio. These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment.
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PMID:Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. 1207 28

In type 2 diabetes, the threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with elevated fasting and postprandial triglycerides and dyslipidemia when compared with the wild type (Ala-54/Ala-54). To assess whether this is the case in patients with type 1 diabetes, who usually do not manifest the metabolic syndrome, we screened 181 patients with similar glycemic control as the type 2 patients. Thirty percent were heterozygous, and 9% were homozygous for the polymorphism. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild type (n = 84), those heterozygous for Ala-54/Thr-54 (n = 44), and those homozygous for the Thr-54 (n = 13) were 1.0 +/- 0.07, 1.1 +/- 0.17, and 1.2 +/- 0.23 mmol/liter, respectively. In addition, there were no differences in total, low-density lipoprotein, high-density lipoprotein, and non-high density lipoprotein cholesterol among the three groups. After a fat load, the postprandial area under the curve of triglyceride in plasma, chylomicrons, and very low-density lipoprotein were similar between the wild type (n = 18) and the Thr-54 homozygotes (n = 12). In conclusion, in contrast to type 2, type 1 diabetes does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene to cause hypertriglyceridemia/dyslipidemia. Insulin resistance could account possibly for this difference.
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PMID:Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene. 1216 3

Different approaches have been proposed to improve the adaptation of Class II restorations, including applying low-elasticity modulus base liners. This in vitro fatigue test (or study) evaluated the influence of the compomer base-lining configuration on restoration adaptation. Direct Class II MOD box-shaped composite restorations with or without base and lining (n=3x8) were placed on intact human third molars with proximal margins 1 mm above or under the CEJ. The compomer (Dyract) was applied as a 1 mm-thick lining or as a base, closing proximo-gingival margins. Marginal adaptation was assessed before and after each phase of mechanical loading (250,000 cycles at 50N, 250,000 cycles at 75N and 500,000 cycles at 100N); internal adaptation was evaluated after test completion. Gold-sputtered resin replicas were observed in the SEM and restoration quality evaluated in percentages of continuity (C) at the margins and within the internal interface after sample section. Mechanical loading did not influence adaptation to enamel, while it adversely affected restoration adaptation to dentin for the full composite and compomer-base restorations (C varied, respectively, from 95.2 to 75.3% and from 98.0 to 10.6%). The internal adaptation quality showed the same general trend, however, with reduced scores of continuity. In this experimental condition, application of a low elasticity modulus layer under the restorative material proved advantageous but the compomer should not contact the gingival margins.
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PMID:Marginal and internal adaptation of stratified compomer-composite Class II restorations. 1221 70

The physiologic effects of the chromogranin A peptide fragment, pancreastatin, were studied in six healthy Caucasian men, ages 25-46 years. Synthetic pancreastatin (human chromogranin A(273-301)-amide) was infused into the brachial artery of each subject to achieve a local concentration of approximately 200 nM over 15 minutes. Forearm blood flow was measured by strain-gauge plethysmography while (A-V)(glucose) was monitored by arterial and venous sampling. Pancreastatin infusion significantly reduced forearm glucose uptake (mean reduction +/- 1 SEM, 54 +/- 15%; P = 0.028) but did not alter forearm blood flow-indicating a metabolic, rather than hemodynamic, effect. Simultaneous infusion of pancreastatin with insulin (0.1 mU/kg/min) did not diminish insulin-induced forearm glucose uptake, suggesting pancreastatin is not simply a negative insulin modulator. The results of this study suggest that pancreastatin may contribute to the dysglycemia associated with type 2 diabetes and essential hypertension, two common human disease states in which plasma pancreastatin levels are elevated.
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PMID:Studies of the dysglycemic peptide, pancreastatin, using a human forearm model. 1243 74

Direct class II composite restorations still represent a challenge, particularly when proximal limits extend below the CEJ. The aim of this in vitro study was to evaluate the influence of the type of adhesive and the delay between adhesive placement and composite insertion on restoration adaptation. Direct class II MOD box-shaped composite restorations (n=8 per group) were placed on intact human third molars, with proximal margins 1mm above or under CEJ. All cavities were filled with a horizontal layering technique, immediately after adhesive placement (IP) or after a 24h delay (DP). A filled three-component adhesive (OptiBond FL: OB) and a single-bottle, unfilled one (Prime & Bond 2.1: PB) were tested. Marginal adaptation was assessed before and after each phase of mechanical loading (250000 cycles at 50 N, 250000 cycles at 75 N and 500000 cycles at 100 N); internal adaptation was evaluated after test completion. Gold-plated resin replicas were observed in the SEM and restoration quality evaluated in percentages of continuity (C) at the margins and within the internal interface, after sample section. Adaptation to beveled enamel proved satisfactory in all groups. After loading, adaptation to gingival dentin degraded more in PB-IP (C=55.1%) than PB-DP (C=86.9%) or OB-DP (C=89%). More internal defects were observed in PB samples (IP: C=79.2% and DP: C=86.3%) compared to OB samples (IP: C=97.4% and DP: C=98.3%). The filled adhesive (OB) produced a better adaptation than the 'one-bottle' brand (PB), hypothetically by forming a stress-absorbing layer, limiting the development of adhesive failures. Postponing occlusal loading (such as the indirect approach) improved also restoration adaptation.
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PMID:Marginal and internal adaptation of class II restorations after immediate or delayed composite placement. 1245 Jul 17

Autosomal dominant polycystic kidney disease (ADPKD) is a common renal disease without an effective therapeutic intervention to delay renal failure. Within kindreds, renal dysfunction often develops at a similar age in affected individuals, although there are known modifying factors. Two kindreds with ADPKD have shown a striking pattern of delayed onset of renal insufficiency in those individuals also suffering from type 2 diabetes mellitus. Eight nondiabetic patients with ADPKD had onset of dialysis or renal death at ages 38-52 years, (mean +/- SEM 46 +/- 1.9, n = 7) as compared with four diabetics who started dialysis or are still off dialysis at the age of 61 +/- 2.8 years (p < 0.01). Two of the four diabetics still have reasonable renal function at age 61 and 66. The diabetes was diagnosed at age 32 +/- 2 years and was treated with oral hypoglycemics for 19 +/- 2 years before institution of insulin. Cardiovascular disease dominated the clinical picture in the diabetics. In conclusion, onset of renal failure in ADPKD was delayed for over 15 years in individuals who also suffered from type 2 diabetes mellitus, in two ADPKD kindreds. Possible mechanisms are discussed, including glibenclamide inhibition of the cystic fibrosis transmembrane conductance regulator. The striking delay associated with type 2 diabetes mellitus in ADPKD induced renal failure should be evaluated further.
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PMID:Does type 2 diabetes mellitus delay renal failure in autosomal dominant polycystic kidney disease? 1247 2

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol from inactive cortisone in liver and adipose tissue. Inhibition of 11 beta-HSD1 offers a novel potential therapy to lower intracellular cortisol concentrations and thereby enhance insulin sensitivity and hepatic lipid catabolism in type 2 diabetes, obesity, and hyperlipidemia. We evaluated this approach using the nonselective 11 beta-HSD inhibitor, carbenoxolone, in healthy men and lean male patients with type 2 diabetes. Six diet-controlled nonobese diabetic patients with hemoglobin A(1c) less than 8%, and six matched controls participated in a double-blind, cross-over comparison of carbenoxolone (100 mg every 8 h, orally, for 7 d) and placebo. They were admitted overnight for infusions of insulin (as required to maintain arterialized plasma glucose of 5.0 mM) and [13C6]glucose. Glucose kinetics were measured in the fasted state from 0700-0730 h, during a 3-h euglycemic hyperinsulinemic clamp (including somatostatin infusion and replacement of physiological GH and glucagon levels), and during a 2-h euglycemic hyperinsulinemic clamp with a 4-fold increase in glucagon levels. Data are the mean +/- SEM. Carbenoxolone had the expected effects of raising blood pressure and lowering plasma potassium. Carbenoxolone reduced total cholesterol in healthy subjects (5.25 +/- 0.34 vs. 4.78 +/- 0.40 mM; P < 0.01), but had no effect on other serum lipids or on cholesterol in diabetic patients. Carbenoxolone did not affect the rate of glucose disposal or the suppression of free fatty acids during hyperinsulinemia. However, carbenoxolone reduced the glucose production rate during hyperglucagonemia in diabetic patients (1.90 +/- 0.2 vs. 1.53 +/- 0.3 mg/kg x min; P < 0.05). This was attributable to reduced glycogenolysis (1.31 +/- 0.2 vs. 1.01 +/- 0.2 mg/kg x min; P < 0.005) rather than altered gluconeogenesis. These observations reinforce the potential metabolic benefits of inhibiting 11 beta-HSD1 in the liver of patients with type 2 diabetes. Further studies in obesity and hyperlipidemia are now warranted. However, clinically useful therapeutic effects will probably require selective 11 beta-HSD1 inhibitors that lower intraadipose cortisol levels and enhance peripheral glucose uptake.
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PMID:Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. 1251 67

Impaired fasting glucose (IFG) is commonly seen in the US population. Approximately 20% of patients with IFG can progress to develop type 2 diabetes mellitus (DM-2) within 1 year. In the recent diabetes prevention study, lifestyle changes reduced the progression to only 8% per year, and metformin reduced the progression from IFG to DM-2 from 20% to 11% per year. Sulfonylurea therapy in DM-2 increases beta-cell function and fails to accelerate the 4% loss in function observed per year. Low-dose sulfonylurea therapy for IFG may be an effective treatment to delay the onset of type 2 diabetes if the treatment does not cause hypoglycemia. A very low dose of glyburide (20 microg/kg body weight) was given orally to 15 nondiabetic volunteers in an attempt to describe its effects on glucose production rates (GPR), blood glucose concentrations, and conterregulatory hormone profile. Six of the volunteers had IFG (mean +/- SEM, 115 +/- 1.8 mg/dL), and 9 had a normal fasting glucose (NFG) (94 +/- 2.3 mg/dL). Fasting blood glucose (FBG) decreased more in IFG after glyburide when compared with the NFG group (29% +/- 2.4% v 17% +/- 3.5%, P <.05). Patients with IFG had a larger insulin response to glyburide than those with NFG (17.7 +/-3 v 10.7 +/- 2.9 microU/mL; P <.05). The IFG patients also had a greater decrease in GPR (19% +/- 4%) than seen with the normals (12% +/- 3%, P <.05). The steeper decrease in GPR may have been due to a greater insulin response to oral glyburide in those with IFG. Low-dose glyburide increases insulin's effect on the liver.
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PMID:Low-dose oral glyburide reduces glucose production rates in patients with impaired fasting glucose. 1270 Oct 50


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