Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acetylator phenotypes of 200 Saudi diabetics and an equal number of control subjects of the same origin were determined by measuring the peak height ratio of two urinary caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX), using a simplified high-performance liquid chromatographic method. Urine samples were collected from the diabetics and the control subjects who regularly drink coffee, tea, or caffeinated beverages as part of their normal daily diet. The patients were classified as either type 1 (insulin-dependent) (28 patients) or type 2 (insulin-independent) diabetics (172 patients) according to standard criteria. The reproducibility of acetylator phenotype was established by examining the peak height ratio of AFMU/1MX in 18 diabetics and 6 control subjects on different days. Significant differences in the proportion of rapid acetylators were observed between type 1 (53.6%) and type 2 (33.7%) diabetics (P < or = .0436), and between the control group (26%) and the overall diabetics (36.5%) (P < or = .024) or those with type 1 disease (P < or = .0028). Also, there was a significant (P < or = .0436) association between rapid acetylator status and type 1 diabetes mellitus.
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PMID:N-acetylation polymorphism and diabetes mellitus among Saudi Arabians. 144 97

The methylxanthine theophylline increases intrahepatic c-AMP and c-AMP mediates the hepatic glucose response to adrenaline and glucagon. Intravenous theophylline increases glucose recovery during acute insulin-induced hypoglycaemia and caffeine increases hypoglycaemia awareness and glucoregulatory hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m(-2)) after 2 weeks' oral therapy with Euphyllin Retard (theophylline) or placebo. Plasma glucose nadir was 2.54 (2.31-2.77) mmol l(-1) after Euphyllin Retard and 2.27 (2.05-2.48) mmol l(-1) after placebo (mean difference 0.26 (0.05-0.58) mmol l(-1), p = 0.09) for healthy control subjects and 2.56 (2.07-3.04) mmol l(-1) and 2.19 (1.37-2.65) mmol l(-1) (mean difference 0.38 (0.12-0.63) mmol l(-1), p = 0.01), respectively, for diabetic patients. The area under the glucose curve was greater after theophylline treatment for healthy control subjects (p = 0.0292) and for diabetic patients (p = 0.0241) but there were no concomitant significant increases in plasma c-AMP or in endogenous glucose production rate. Whether the increase in glucose recovery is large enough to suggest that chronic theophylline administration will protect against insulin-induced hypoglycaemia remains unsettled.
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PMID:Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus. 968 2

Caffeine, 1,3,7trimethylxanthine, is used by 80% of the adult population of the world in its various forms. Even the simple pleasure of consuming this socially acceptable drug has implications for the person with diabetes mellitus. Caffeine may increase an individual's sensitivity to hypoglycemia through the combined effects of reducing substrate delivery to the brain via constriction of the cerebral arteries, whilst simultaneously increasing brain glucose metabolism and augmenting catecholamine production. This article summarizes the evidence supporting the hypothesis that caffeine influences the perception of and physiological response to hypoglycemia. Under laboratory conditions, acute ingestion of caffeine markedly enhances the symptomatic and sympathoadrenal responses to hypoglycemia in both healthy volunteers and patients with type 1 diabetes. Recently a study of free-living people with type 1 diabetes showed that caffeine consumption increased the awareness of hypoglycemia. Caffeine has been associated with a number of negative effects and addiction. Most serious of these associations are ischemic heart disease and hypertension, the relationships have not been clearly established and the evidence to date is controversial. Thus we conclude that in modest doses, caffeine may be a useful adjuvant therapy for patients with hypoglycemia unawareness. For once here is a therapy which is inexpensive, safe, and remarkably popular with its consumers.
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PMID:The best defense against hypoglycemia is to recognize it: is caffeine useful? 1147 92

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, Ad5-FGF4, adeno-Interferon gamma, AE-941, AERx, alemtuzumab, alicaforsen sodium, almotriptan, alpharadin, anakinra, anatumomab mafenatox, ANG-453, anti-CTLA-4 Mab, AP-12009, aprepitant, aripiprazole, arsenic trioxide, astemizole, atlizumab, atomoxetine hydrochloride; Bevacizumab, BG-9928, BMS-188667, botulinum toxin type B, BufferGel; Caffeine, CDP-870, cetuximab, cilomilast, ciluprevir, clofarabine, continuous erythropoiesis receptor activator, CP-461; Darbepoetin alfa, deferasirox, desloratadine, desoxyepothilone B, diflomotecan, dolasetron, drotrecogin alfa (activated), duloxetine hydrochloride; ED-71, efalizumab, efaproxiral sodium, EKB-569, eletriptan, EMD-72000, enfuvirtide, erlotinib hydrochloride, escitalopram oxalate, etoricoxib; Fampridine, ferumoxytol, fondaparinux sodium; Gadofosveset sodium, gastrazole, gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride glutamine; hLM609, HSPPC-96, human insulin; IDD-1, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; Keratinocyte growth factor; Lapatinib, laquinimod, LDP-02, LE-SN38, levetiracetam, levosimendan, licofelone, liposomal doxorubicin, liposomal NDDP, lopinavir, lumiracoxib, LY-156735; Morphine hydrochloride, morphine-6-glucuronide, motexafin gadolinium, MS-27-275, MVA-5T4, MVA-Muc1-IL-2; Nemifitide ditriflutate, neridronic acid nitronaproxen, NSC-683864, NSC-703940, NVP-LAF-237; Oblimersen sodium, ocinaplon, oncomyc-NG, OPC-28326, ortataxel, ospemifene; Palonosetron hydrochloride, PEG-filgrastim peginterferon alfa-2(a), peginterferon alfa-2b, pegsunercept, pemetrexed disodium, pregabalin, prilocaine, pyridoxamine; RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, recombinant human ApoA-I milano/phospholipid complex; SB-715992, soblidotin, sodium dichloroacetate, St. John's Wort extract; TAS-102, terfenadine, TG-1024, TG-5001, 4'-Thio-ara-C, tipranavir, topixantrone hydrochloride, trabectedin, transdermal selegiline, trimethoprim, troxacitabine, TT-232; Vatalanib succinate, vinflunine; Ximelagatran; Ziprasidone hydrochloride, Zoledronic acid monohydrate.
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PMID:Gateways to clinical trials. 1498 42

Using biochemical/pharmacological approaches, we previously showed that type 2 ryanodine receptors (RyR2) become dysfunctional in hearts of streptozotocin-induced type 1 diabetic rats. However, the functional consequence of this observation remains incompletely understood. Here we use laser confocal microscopy to investigate whether RyR2 dysfunction during diabetes alters evoked and spontaneous Ca(2+) release from the sarcoplasmic reticulum (SR). After 7-8 weeks of diabetes, steady-state levels of RyR2 remain unchanged in hearts of male Sprague-Dawley rats, but the number of functional receptors decreased by >37%. Interestingly, residual functional RyR2 from diabetic rat hearts exhibited increased sensitivity to Ca(2+) activation (EC(50activation) decreased from 80 microM to 40 microM, peak Ca(2+) activation decreased from 425 microM to 160 microM). When field stimulated, intracellular Ca(2+) release in diabetic ventricular myocytes was dyssynchronous (non-uniform) and this was independent of L-type Ca(2+) currents. Time to peak Ca(2+) increased 3.7-fold. Diabetic myocytes also exhibited diastolic Ca(2+) release and 2-fold higher frequency of spontaneous Ca(2+) sparks, albeit at a lower amplitude. The amplitude of caffeine-releasable Ca(2+) was also lower in diabetic myocytes. RyR2 from diabetic rat hearts exhibited increased phosphorylation at Ser2809 and contained reduced levels of FKBP12.6 (calstablin2). Collectively, these data suggest that RyR2 becomes leaky during diabetes and this defect may be responsible to the reduced SR Ca(2+) load. Diastolic Ca(2+) release could also serve as a substrate for delayed after-depolarizations, contributing to the increased incidence of arrhythmias and sudden cardiac death in type 1 diabetes.
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PMID:Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced diabetic rats. 1702 51

Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede diastolic heart failure. However, mechanisms that underlie diastolic dysfunction during diabetes are not well understood. We tested the hypothesis that isolated diastolic dysfunction is associated with impaired myocardial Ca(2+) handling during type 1 diabetes. Streptozotocin-induced diabetic rats were compared with age-matched placebo-treated rats. Global left ventricular myocardial performance and systolic function were preserved in diabetic animals. Diabetes-induced diastolic dysfunction was evident on Doppler flow imaging, based on the altered patterns of mitral inflow and pulmonary venous flows. In isolated ventricular myocytes, diabetes resulted in significant prolongation of action potential duration compared with controls, with afterdepolarizations occurring in diabetic myocytes (P < 0.05). Sustained outward K(+) current and peak outward component of the inward rectifier were reduced in diabetic myocytes, while transient outward current was increased. There was no significant change in L-type Ca(2+) current; however, Ca(2+) transient amplitude was reduced and transient decay was prolonged by 38% in diabetic compared with control myocytes (P < 0.05). Sarcoplasmic reticulum Ca(2+) load (estimated by measuring the integral of caffeine-evoked Na(+)-Ca(2+) exchanger current and Ca(2+) transient amplitudes) was reduced by approximately 50% in diabetic myocytes (P < 0.05). In permeabilized myocytes, Ca(2+) spark amplitude and frequency were reduced by 34 and 20%, respectively, in diabetic compared with control myocytes (P < 0.05). Sarco(endo)plasmic reticulum Ca(2+)-ATPase-2a protein levels were decreased during diabetes. These data suggest that in vitro impairment of Ca(2+) reuptake during myocyte relaxation contributes to in vivo diastolic dysfunction, with preserved global systolic function, during diabetes.
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PMID:Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes. 1776 17

Coffee consumption has been associated with a lower risk of type 2 diabetes. This association does not depend on race, gender, geographic distribution of the study populations, or the type of coffee consumed (i.e., caffeinated or decaffeinated). This review discusses the strength of this relationship, examines the possibility that the pattern of coffee consumption could influence the association, and evaluates the possible relationship between coffee consumption and other risk factors associated with diabetes. Particular attention is paid to the identification, on the basis of the scientific evidence, of the possible mechanisms by which coffee components might affect diabetes development, especially in light of the paradoxical effect of caffeine on glucose metabolism. In addition to the role of coffee in reducing the risk of developing type 2 diabetes, the possible role of coffee in the course of the illness is explored. Finally, the possibility that coffee can also affect the risk of other forms of diabetes (e.g., type 1 diabetes and gestational diabetes) is examined.
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PMID:Role of coffee in modulation of diabetes risk. 2245 94

Caffeine is a substance that has been used in our society for generations, primarily for its effects on the central nervous system that causes wakefulness. Caffeine supplementation has become increasingly more popular as an ergogenic aid for athletes and considerable scientific evidence supports its effectiveness. Because of their potential to alter energy metabolism, the effects of coffee and caffeine on glucose metabolism in diabetes have also been studied both epidemiologically and experimentally. Predominantly targeting the adenosine receptors, caffeine causes alterations in glucose homeostasis by decreasing glucose uptake into skeletal muscle, thereby causing elevations in blood glucose concentration. Caffeine intake has also been proposed to increase symptomatic warning signs of hypoglycemia in patients with type 1 diabetes and elevate blood glucose levels in patients with type 2 diabetes. Other effects include potential increases in glucose counterregulatory hormones such as epinephrine, which can also decrease peripheral glucose disposal. Despite these established physiological effects, increased coffee intake has been associated with reduced risk of developing type 2 diabetes in large-scale epidemiological studies. This review paper highlights the known effects of caffeine on glucose homeostasis and diabetes metabolism during rest and exercise.
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PMID:Caffeine and glucose homeostasis during rest and exercise in diabetes mellitus. 2385 68

The prevalence of diabetes is growing globally, and with no current cure for the disease, management is focused on optimizing blood glucose control to limit complications. The purpose of this review was to examine the effect of caffeine intake on blood glucose levels in people with diabetes. Electronic searches were completed using Pub Med, CINAHL, and Web of Science using the search terms "coffee and insulin," "caffeine and insulin," "caffeine and diabetes," "caffeine and type 1 diabetes," "caffeine and type 2 diabetes," and "caffeine and glycemia." Seven trials were found to meet the search criteria. Five of the 7 studies suggest caffeine intake increases blood glucose levels, and prolongs the period of high blood glucose levels. Future research should focus on larger clinical trials to confirm the relationship and mechanism of action related to caffeine intake and glycemic control in individuals with diabetes.
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PMID:The effect of acute caffeine intake on insulin sensitivity and glycemic control in people with diabetes. 2893 43

We report the case of a patient with type 1 diabetes who developed acute severe diabetic ketoacidosis following ingestion of an energy supplement containing caffeine. Some 95% of the US adult population consume caffeine, and the general perception is that there are no negative consequences for health. The upper limit of safe consumption is less than 400 mg per day. However, acute ingestion of high doses of caffeine may cause significant metabolic changes that can be fatal. Here the patient consumed a toxic dose of caffeine causing unpleasant and puzzling symptoms, vomiting and, following omission of his long-acting basal insulin, severe diabetic ketoacidosis. As the sports nutrition market continues to expand, providers and manufacturers have a responsibility to give clear and accurate dosing instructions as well as side effect profiles for their products, particularly for diabetic patients.
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PMID:Caffeine Toxicity Following Ingestion of an Exercise Supplement by a Patient with Type 1 Diabetes. 3075 83


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