THE Diabetes DAILYNEWS
for

(CONCEPTS)

Reload The National Diabetes Center Frames



HEADLINES[roughly chronological order]

 

TNF-[alpha] concentration is associated with degrees of early atherosclerosis” (European Heart Journal [2002] 23(5):376-383)

Increased circulating level of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) may be an important causative factor of hypofibrinolysis in patients with type 2 diabetes, obesity and insulin resistance” (The Journal of Clinical Endocrinology & Metabolism {2002]. 87: 660-665)

“Atorvastatin Lowers C-Reactive Protein and Improves Endothelium-Dependent Vasodilation in Type 2 Diabetes Mellitus” (The Journal of Clinical Endocrinology & Metabolism [2002] 87: 563-568)

“In CHD, vWF and tPAag - but not thrombomodulin - are independent markers of atherosclerosis” (Thrombosis Research [2002] 105(1):25-31 )

 “Feeding old rats high levels of key mitochondrial metabolites can ameliorate oxidative damage, enzyme activity, substrate-binding affinity, and mitochondrial dysfunction" (Proc. Natl. Acad. Sci. USA, [2002] 99:1876-1881)

Defective Akt activation is associated with glucose- but not glucosamine-induced insulin resistance (Am J Physiol [2002] 282: e497-506)

Merck's small molecular insulin mimetics reduce food intake and body weight and prevent development of obesity (Nature Medicine [2002] 8:179-183)

Angptl3 probably regulates lipid metabolism in animals” (Nature Genetics [2002] 30:151-157)

Oral Administration of an Apo A-I Mimetic Peptide Synthesized From D-Amino Acids Dramatically Reduces Atherosclerosis in Mice Independent of Plasma Cholesterol” (Circulation [2002]105:290)

In obese women, endothelial activation correlates with visceral body fat and weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction.” (Circulation [2002; 10:1161)

“Estrogen Monotherapy Reduces Risk of Carotid IMT - and Improves Glucose Control(Ann Intern Med. [2001] 135:939-953)

Islet Neogenesis Associated Protein (INGAP) Peptide Now in Human Clinical Trials for Type 1 DM (Intellihealth, [2002] Jan 14)

Inflammation may be an etiologic factor for diabetes in women”  (American Journal of Epidemiology [2002]155: 57-64)

Increased resistin expression in abdominal fat could explain the increased risk of type 2 diabetes associated with central obesity” (Lancet [2002] 359)

Perilipin Gene is Potentially Involved in the Rupture of Human Atherosclerotic Plaques (Circulation Research. [2001] 89:547.)

Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production [per adipocyte mass], a resistance to diet-induced obesity, as well as a tendency toward insulin resistance (Proc. Natl. Acad. Sci. USA [2001] 98: 6494-6499)

Triglycerides >200 mg/dl (But Not Triglyceride Reduction) Strongly Associate with Stroke Risk in BIP (Circulation [2001] 104:2892)

"A major Israeli study of 3090 patients - the Bezafibrate Infarction Prevention trial - showed no significant reduction in fatal or non-fatal MI or sudden death from triglyceride reduction" (Circulation [2000] 102:21)

 Increased adipocyte 11 HSD-1 activity mimics visceral obesity and the metabolic syndrome.(Science [2001] 294: 2071-2072)

Treatment of newly diagnosed type 1 diabetes with DiaPep277 seems to preserve endogenous insulin production (Lancet [2001] 358: 1749)

Elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly and independently of other cardiovascular risk factors.” (Stroke. [2001] 32:2575)

Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals.” (JAMA. [2001]286:1882-1885) 
"2-microglobulin is a type 1 susceptibility gene" (Proc. Natl. Acad. Sci. USA, [2001] 98: 11533-11538)

"Novel Advanced Glycation End-Product Crosslink Breaker Improves Arterial Compliance" (Circulation. [2001]104:1464.)

"An insulin-sensitive phosphatidylinositol 3-kinase/Akt pathway may promote carcinogenesis via ranslocation of Mdm2 from the cytoplasm to the nucleus" (PNAS [2001] 98 11598-11603)

"Disruption of Sur2-containing KATP channels [?hyperpolarization -ed.] enhances insulin-stimulated glucose uptake in skeletal muscle" (PNAS [2001] 98 11760-11764)

"Pravastatin Treatment Removes any Increased Effect of LARGE Low-Density Lipoprotein Size upon Coronary Events" (JAMA. [2001] 286:1468-1474)

"Plasma leptin concentration is a novel and independent risk factor for CHD in WOSCOPS" (Diabetologia [2001] 44 (Suppl 1): A315. EASD 37th Annual Meeting, #1209)

"Fasting plasma IL-6 concentrations are positively related to adiposity and negatively related to insulin action"(Obesity Research [2001] 9:414-417 )

"Transcriptional coactivator PGC-1 controls hepatic gluconeogenesis" (Nature [2001] 413: 131 - 138)

"Plasmid Vaccination with Insulin B Chain Prevents Autoimmune Diabetes in Nonobese Diabetic Mice. This effect is dependent upon IL-4" (The Journal of Immunology, [2001] 167: 2950-2955.)

"The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice" (Nature Medicine [2001] 7:1052-1056)

"IKK- May Underly the Inflammatory Etiology of the Dysmetabolic Syndrome " (Science [2001] 293: 1673 - 1677)

"Lamotrigine somewhat effective in reducing painful diabetic neuropathy [NPS 4.2 vs 5.3]" (Neurology [2001] 57:505-509)

"GLP-1 or exendin-4 applied during the neonatal diabetic period exert both short- and long-term beneficial effects on -cell mass recovery and glucose homeostasis" (Diabetes [2001] 50:1562-157)

"More Data that Estrogen is NOT cardio-protective in diabetic women" (Am J Hypertension [2001] 14:699-703)

"Short-term reduction of HbA1c levels does not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control" (Intern Med J [2001] 31: 322–328)

"MI Presaged by Increased HbA1c" (European Heart Journal [2001] 22:1102-1110)

"Insulin Inhibits the Expression of Intercellular Adhesion Molecule-1 by Human Aortic Endothelial Cells through Stimulation of Nitric Oxide" (The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 7 2572-2575)

"Increased PAI-1 in the arterial wall associates with diabetes." (Arteriosclerosis, Thrombosis, and Vascular Biology. [2001]21:1378-1382.)

"Circulating NEFA concentration is an independent risk factor for sudden death in middle-aged men. Fish oils are protective." (Circulation [2001]104:756-761)

"Trans Fatty Acids Increase Risk Of Diabetes in Women" (Am J Clin Nutr [2001] 73(6):1019-1026 )

"Diet and exercise (58%) better than metformin (31%) in delaying type 2 diabetes!" (NIDDK, DPT2 Results, 8 August 2001)

":Diabetic peripheral neuropathy may have a spinal components (Lancet [2001] 358:35-36) +review

"Diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction " (JACC [2000] 38:421-428)

"Inositol Phosphoglycans (IPGs) are Involved in the Reversal of Type 2 Diabetes in Mice by Products of Malaria Parasites" (Mol Genetics Metab [2001] 73: 248-258)

"Acrp30 is a potent insulin enhancer linking adipose tissue and whole-body glucose metabolism." (Nature medicine [2001] 7:947-953)

"Atenolol = less morbidity + equivalent mortality vs. captopril in UKPDS" (Diabetic Medicine [2001] 18 (6), 438-444)

"Insulin resistance in lipoatrophic mice is completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone" (Nature Medicine [2000] 7:941-946)

"Trans fatty acids impair endothelial function (flow mediated dilation) in healthy individuals" (Arteriosclerosis, Thrombosis, and Vascular Biology. [200]1:21:1233.)

"Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a role for inflammation in diabetogenesis." (JAMA. [2001] 286:327-334)

"Tissue-specific deletion of Foxa2 in pancreatic cells results in hyperinsulinemic hypoglycemia" (Genes Dev. [2001} 15:1706-1715)

"Diabetes Death Rate is Increasing" (CDC Press Release, 2001)

"Glycemic Control is Without Effect upon Hepatic Lipase in Type 1 Diabetes" (ADA 61st SS, Abstract #2197-PO, June 2001)

"Gamma Globulin Levels Predict Type 2 Diabetes in the Pima Indian Population" (ADA 61st SS, Abstract #154-PO, June 2001)

"Insulin Resistance Is More Predictive Than Glycaemia of Coronary Heart Disease in a Randomized Controlled Trial of Farglitazar" (ADA 61st SS, Abstract #2159-PO, June 2001)

"Elevated White Blood Cell Count Predicts Type 2 Diabetes in Pima Indians " (ADA 61st SS, Abstract #2266-PO, June 2001

"-cell-directed autoimmunity can be reversed" (J Clin Invest [2001] 108:63-72)

"Dyslipidemia Is Predictive of Macrovascular Events in Type 2 Diabetes While Glycemia Is Not" (ADA 61st SS, Abstract #1910-PO, June 2001)

"Pre-DM subjects may have an increased risk of CVD even prior to the onset of DM" (ADA 61st SS, Abstract #118-OR, Sunday, 24 June 2001 )

"UCP2 correlates with leptin levels and may be a a key component of -cell glucose sensing" (Cell [2001] 105: 745-755)

"Losing Weight Returns Compromised T-Cell Function To Normal " (Clin Endocrinol [2001] 54(3):347-354 )

"Diabetes of short duration is found to be associated with a greater than normal number and size of platelet-fibrin thrombi in the retinal capillaries. " (Diabetes {2001}50:1432-1439)

"Excess diabetic mortality, evident in all age groups, is most pronounced in young people with type1" (BMJ [2001] 322:1389-1393)

"Vigorous control of lipid levels and blood pressure is necessary in patients with type 1 diabetes" (Diabetes [2001] 24:1053-1059)

"Insulin Resistance and a Diabetes Mellitus-Like Syndrome Develops in Mice Lacking the Protein Kinase Akt2 (PKB-)" (Science [2001] 292:1728-1731 )

"Lack of macrophage fatty-acid binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis" (Nature Medicine [2001]7:699-705)

"MSH/ACTH[4-10] reduces adiposity, leptin, and insulin" (JCEM [2000] 86:1144-1148)

"Leptin significantly increases Hormone Sensitive Lipase activity in J774.2 macrophages" (Diabetes [2001] 50:955-961)

"NHLBI Issues NCEP iii Guidelines" (15 May 2001)

"Type 2 diabetes can be delayed by changes in the lifestyles of high-risk subjects." (N Engl J Med [2001] 344:1343-50

"Increased plasminogen activator inhibitor activity and diabetes predict subsequent coronary events in patients with angina pectoris" (Ann Med [2001] 33:206-212)

"Three healthcare organizations agree to common measures for evaluating diabetes care" (AMA press release 26 April 2001)

"PPAR-d (delta) agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X" (PNAS [2001] 98:5306-5311)

"IL-12 locally produced by islet-infiltrating cells plays a critical role in the development of type 1 diabetes" (J Autoimmunity [2001]16:97-104)

"Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation and is impacted by ACE inhibitors" (JACC [2001] 37:1565-1570)

"Insulin beneficial in CHF" (Heart [2001] 85:508-513)

"Metformin prevents pancreatic cancer in hamsters" (GASTROENTEROLOGY [2001] 120:1263-1270)

"Diabetes or hyperglycemia impairs activation of mitochondrial KATP channels during infarction" (AJP - Heart Circ Physiol [2001] 280: Issue 4, H1744-H1750)

"Local [adipocyte] expression of TNF and plasma IL-6 are higher in subjects with obesity-related insulin resistance."(Am J Physiol -Endo/Metab [2001] 280: E745-E751)

"Tumor Necrosis Factor (TNF) impairs insulin signaling through Insulin Receptor Substrate-1 (IRS-1) by activation of a PhosphatidylInositol-3 kinase (PI-3k)/ Serine and threonine kinase c-Akt (cloned from directly transforming murine retrovirus AKT8, isolated from an AKR mouse Thymoma cell line) also known as Rac-alpha -Related to the A and C kinases - or protein kinase B-alpha (Akt)/mammalian Target Of Rapamycin (mTOR) pathway, which is antagonized by [3' phospholipid-] Phosphatase and Tensin Homologue Deleted from Chromosome ten (PTEN or MUTATED IN MULTIPLE ADVANCED CANCERS 1-MMAC1)".....(Proc. Natl. Acad. Sci. USA, [2001] 10.1073/pnas.051042298)

"Pharmacological manipulation of Acetyl-CoEnzymeA Carboxylase-2 may lead to loss of body fat in the context of normal caloric intake" (Science [2001] 291:2613-2616"

"hCMV may be involved in the loss of T cell tolerance to autoantigen GAD65 by a mechanism of molecular mimicry leading to autoimmunity."Proc. Natl. Acad. Sci. USA, [2001] 98, Issue 7, 3988-3991

"Does the Choice of Angiographic Discharge Diabetic Medications - metformin. thiazolidinediones, sulfonylureas, or insulin) - Predict Mortality [Or Does Improper Methodology Obfuscate?]" (JACC [2001] 37 (Suppl. A):299A [1302-163])

"The degree of glycemic control among diabetic patients at the time of their index intervention does not have an impact on long-term outcomes after successful Percutaneous Coronary Revascularization." (Am Heart J [2001]141:117-23.)

"Opening of sarcolemmal KATPchannels underlies ST elevation during ischemia" (Circulation Res. [2000] 87:837)

"Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction" (Circulation [2001}103:1410)

"High dietary glycemic index and high glycemic load are associated with a lower concentration of plasma HDL-C" (Arch Intern Med. [2001]161:572-576

"The 2h-BG is a better predictor of deaths from all causes and cardiovascular disease than is FBG." (Arch Intern Med. [2001] 161:397-404)

"The hormone resistin links obesity to diabetes" (Nature {2001] 409: 307-312)

"Overweight children have higher concentrations of C-reactive protein and higher white blood cell counts than normal weight children, indicating low-grade systemic inflammation, which may predict future cardiovascular disease and diabetes" (Pediatrics [2001] 107:e13)

"Obesity in individuals with a family history of diabetes or hypertension strongly associates with the Insulin Resistance Syndrome" (Genetic Epidemiology [2000] 19: 395-409)

"pDNA vaccination is an effective strategy to prevent IDDM" (The Journal of Immunology [2001] 166: 2122-2132)

"Pravastatin is the latest of anti-atherosclerotic agents to be shown to delay glucose excursions and the development of Diabetes Mellitus" (Circulation. [2001] 103:357)

"Glu)cose-dependent insulin release achieved in non-beta cells" (Science [2000] 290:1959-1962

"Statin Plus Niacin Brings CAD Progression To A 'Standstill'" (AHA Meeting, 14 Nov 2000, New Orleans)

"High-dose vitamin E reduces serum levels of C-reactive protein in diabetes" (Free Radic Biol Med [2000];8:790-792)

"Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice" (Nature Medicine [2000] 6:1115 - 1120)

"'Big Whoop of the Year' Award goes to Joslin&German Weenie-Wonks who used knock-out technology to figure out that insulin is THE PRANDIAL MESSAGE" (Science [2000] 289: 2122-2125)

"Appetite-Stimulating Gene Found on Chromosome 19 and 100% Homologous in Humans and Rats is 81% Homomologous in Earthworms" (EASD Symposium on AP, Wednesday 20 Sep 2000)

"Niacin Safe and Effective for Diabetic Dyslipidemias" (JAMA [2000] 284:1263-1270)

"Results support the hypothesis that adenosine receptor activation primes the opening of mitochondrial KATP channels in a cardioprotective, protein kinase C-dependent manner" (Circulation [2000] 102:800)

"Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean" (Nature [2000] 406:415 - 418 )

"Protein Kinase C action decreases the Hill coefficient of ATP binding to cardiac KATP channels, thereby increasing their open probability at physiological ATP concentrations" (PNAS [2000] 10:1073)

"Yet another fibrate study shows coronary effect with no survival benefit" (G. Steiner, MD; WHO, Diabetes Atherosclerosis Intervention Study -DAIS, 26 Jun 2000)

"Rosiglitazone Improves beta-Cell Function as Measured by Proinsulin/Insulin Ratio in Patients with Type 2 Diabetes "(ADA 60th Scientific Sessions [2000], Abs #495)

"Plasma ICA, GADAb, and PBMC reactivity to human fetal pancreatic proteins in transplant recipients is most consistent with reactivation of type 1 disease" (Transplantation [2000] 69(1):166-72)

"A high dietary glycemic load from refined carbohydrates increases the risk of CHD, independent of known coronary disease risk factors" (American J Clin Nutrition [2000] 71:1455-1461)

"CD26 worsens blood glucose regulation by proteolytically inactivating GLP-1 thereby decreasing insulin secretion"(Proc. Natl. Acad. Sci. USA[2000], 10.1073)

"Either glyburide or mitochondrial K(ATP) channel blocker 5-hydroxydecanoate abolish cardioprotection by YM934 in a concentration-dependent manner" J Pharmacol Exp Ther [1999] 291(2):710-716

"Pexiganan cream 1% provides a high clinical response rate for infected diabetic foot ulcers" (ADA 59th Scientific Sessions [1999], Abs #517)

"CLA-1/SR-BI Is Expressed in Atherosclerotic Lesion Macrophages and Regulated by Activators of Peroxisome Proliferator-Activated Receptors "(Circulation[2000]101:2411)

"Atherogenic CD36 expression by oxidized LDL and IL-4 by a common signaling pathway is dependent on protein kinase C and PPAR-gamma " (J.Lipid Res. [2000] 41:688-696)

"Factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer" (JAMA [2000]283:2552-2558)

"Acute hyperglycemia increases circulating sICAM-1 levels in normal subjects, whereas the correction of hyperglycemia with insulin or l-arginine supplementation restored to normal levels the increased plasma sICAM-1 levels of type 2 diabetic patients" (Circulation [2000] 101:2247)

"GlucoWatch Biographer™ Finally Approved (!)" (9 May 2000, Cygnus, Inc.)

"Glycation of CD59 may form the molecular basis for a link between complement and the vascular complications of diabetes" (PNAS [2000] 97:5450-5455)

"ACE Receptor Blockers are NOT superior to ACE Inhibitors (in Heart Failure) - BUT ARE THEY EQUIVALENT ?" (Lancet [2000] 355:1582-1587)

"NDC ISSUES WARNING AGAINST THE USE OF HIGHER SULFONYLUREA DOSAGES" (NDC, 3 May 2000)

"Serum leptin is elevated in patients with coronary artery disease" (International Journal of Obesity and related metabolic disorders [ 2000] 24 :Pages 369 - 375]

"HCV-infected subjects are four times more likely to have type 2 diabetes than those without HCV"(DG News, 14 April 2000)

"Once-Daily Glargine Insulin [Lantus-tm] Approved for Injection"( FDA Label, 24 April 2000)

"Hyperinsulinemia modest association with CV mortality is largely explained by obesity, hypertension, and dyslipidemia" (Arch Intern Med. [2000]160:1160-1168)

"Microalbuminuria and gross proteinuria significantly associate with subsequent mortality from all causes." (Arch Intern Med. [2000]160:1093-1100)

American Ginseng (Panax quinquefolius L) Reduces Postprandial Glycemia in Nondiabetic Subjects and Subjects With Type 2 Diabetes Mellitus  (Arch Int Med [2000]:Vol 160 No. 7)

"Low Cardiorespiratory Fitness and Physical Inactivity Predict Mortality in Men with Type 2 Diabetes" (Annals Int Med [2000] 133:)

"Glucosamine Supplements May Raise Diabetes Risk" (Experimental Biology 2000 Session, San Diego, CA, 21 April 2000)

"Targeted Overactivity of beta- Cell KATP Channels Induces Profound Neonatal Diabetes" (Cell [2000] 100:534-654)

"Normalizing mitochondrial superoxide production blocks the three major pathways of hyperglycaemic endothelial damage" (nature [2000] 404:787-790

"Cardiologists beware:- diabetics should have CABG and NOT PTCA for coronary lesions" (J Am Coll Cardiol [2000]35:1122-1133).

"The odds ratio for 5-year mortality for hyperhomocysteinemia inthe Hoorn Study was 1.34 (0.87 to 2.06) in nondiabetic subjects and 2.51 (1.07 to 5.91) in diabetic subjects (P=0.08 for interaction)" Circulation [2000]101:1506

"TGF-beta-1 appears to correlate with hypertension in blacks" Proc. Natl. Acad. Sci. [2000] 97: 3479-3484

"Beta-blockers inhibit insulin release increasing risk of diabetes [while improving overall survival]" The New England Journal of Medicine [2000] 342 (#13)

"Prolonged hyperlipidemia - independent of insulin - may contribute to increased fat metabolism and storage as a result of FAT/CD36, PPAR-2, leptin, UCP-2, UCP-3, and TNF-alpha induction" Diabetes [2000]49:319–324"

"Rezulin removed from the US market after FDA CDER Woodcock Meeting 4PM Tuesday 21 March"


"Avandia Approved for Marketing in the EU"

"Sestamibi Stress test predicts future events and mortality in diabetics equally among the sexes IN THOSEWITH PREEXISTING CHD" [49th Annual Scientific Session of the American College of Cardiology (ACC), Anaheim, March 1999]

"New data suggest that atherogenic changes in the prediabetic state are mainly seen in insulin-resistant subjects and that strategies to prevent type 2 diabetes might focus on insulin-sensitizing interventions rather than interventions that increase insulin secretion because of potential effects on cardiovascular risk. "(Circulation [2000] 101:975)

"Noninvasive monitoring now feasible also using ultrasound technology"(Nature Medicine [March 2000] Volume 6 Number 3 pp 347-350)

"Initial reversal of insulin-dependent diabetes seen using islets generated in vitro from pancreatic stem cells" (Nature Medicine [March 2000] Volume 6 Number 3 pp 278 - 282)

:Sino American Health Products, Inc., Issues a National Recall of Herbal Products Due to the Presence of the Undeclared Drugs Glyburide and Phenformin." (24 Feb 2000)

"FDA approves Animas Insulin Pump"...(23 Feb 2000)

"Growth hormone therapy in children is associated with a *6-fold* higher risk of type 2 diabetes (344/100000 years) AND the type 2 diabetes does NOT resolve after GH therapy is stopped...."(Lancet[2000]355:610-613)

"The change from resting values in diastolic but not systolic blood pressure during exercise correlates with serum cholesterol (R>0.47, P<0.0001 for each workload) and insulin resistance (R>0.38, P<0.01 for each workload)"......(Circulation[2000] 101:611)

"JAMA publishes *VA VOODOO* study - utilizing such inane concepts as *utility index* of blindness and *quality adjusted life years* as well as innumerable assumptions predicting *days of blindness* - to suggest that yearly visual screens in type 2 patients are not cost-effective...."(JAMA [2000]283:889-896)

"Insulin therapy improves endothelium-dependent and -independent vasodilatation. These data support the idea that insulin therapy has beneficial rather than harmful effects on vascular function" (Arteriosclerosis,Thrombosis and Vascular Biology[2000]20:545)...."

"In multivariate Cox models, the age-adjusted hazard ratio for insulin resistance factor during the 22-year follow-up was 1.28 (95% CI 1.10 to 1.50) with regard to CHD risk and 1.64 (95% CI 1.29 to 2.08) with regard to stroke risk. Lipid factor predicted the risk of CHD but not that of stroke, and lifestyle factor predicted a reduced CHD risk. Factor analysis including only 6 risk factor variables proposed to be central components of insulin resistance syndrome (body mass index, subscapular skinfold, AUC insulin, AUC glucose, mean blood pressure, and triglycerides) produced only a single insulin resistance factor that predicted the risk of CHD and stroke independently of other risk factors" (Arteriosclerosis,Thrombosis and Vascular Biology[2000]20:538)

"Lectin-like Oxidized-LDL (OxLDL) Receptor (LOX-1) is a major receptor for OxLDL in vascular smooth muscle cells as in endothelial cells (VSMC). Lysophosphatidyl choline (LPC) enhances the expression of LOX-1 which suggests that OxLDL and LPC might progressively change the function of VSMC and accelerate atherogenesis in vivo (FEBS [2000] 467:217-220)

"Glucose increases pancreatic levels of preprosomatostatin I mRNA in vivo, in concert with elevated plasma somatostatin levels, and in vitro. Glucose-stimulated expression of preprosomatostatin I mRNA requires the uptake, phosphorylation, and subsequent metabolism of the sugar in pancreatic islets. These results suggest that glucose modulates both the production and release of somatostatin"(FEBS[2000]465:116-118)";

"Platelet-derived thrombogenesis in stable coronary patients associates weakly [but independently] with blood glucose (R2 = 0.19, p < 0.008), and apo-B (R2 = 0.18, p = 0.002) (JACC[2000]35:300-307)";

"LDL particle size and LDL vitamin E may associate with conduit and resistance vessel endothelial vasodilator function in type 1 diabetes. Further work will be required to prove cause and effect (JACC [2000]35:292-299)

"It seems appropriate to question the wisdom of recommending that all Americans should replace dietary saturated fat with CHO(The American Journal of Cardiology{2000], 85:1:45-48).....";


"Marine omega-3 fatty acids improve large artery endothelium-dependent dilation in subjects with hypercholesterolemia without affecting endothelium-independent dilation"
(JACC [2000]35:265-270)

"Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.....";

"Some patients with idiopathic type 1 diabetes have a nonautoimmune, fulminant disorder characterized by the absence of insulitis and of diabetes-related antibodies, a remarkably abrupt onset, and high serum pancreatic enzyme concentrations. (N Engl J Med {2000] 342:301-7.)

"Insulin treatment in type 2 diabetes induces profound metabolic modifications of lipoprotein, resulting in significant decrease of the intravascular residence time of very low density lipoprotein, intermediate density lipoprotein and low density lipoprotein particles. This is likely to make these particles less harmful. (Diabetologia [2000] 43: 27-35)

"Cardiovascular risk and risk of future diabetes increase continually with increasing FPG, and there is no threshold value on which to base a definition of IFG. If a lower limit of ~5.8 mmol/l is used, the category defines a group more similar to the group with impaired glucose tolerance, with regard to total prevalence and the risk of subsequent diabetes.....";

"In normal glucose tolerant offspring of type 2 diabetics, PAI-1 activity was correlated with plasma PAI-1 antigen level (r = 0.40, P = 0.02), fibrinogen (r = 0.45, P = 0.01), and HDL cholesterol (r = –0.36, P = 0.04). However, tPA antigen level, fasting and postload plasma glucose and insulin, total cholesterol, triglycerides, WHR, and BMI did NOT correlate with PAI-1 activity.....";

"Nitric Oxide (NO) directly activates mitoKATP channels and potentiates the ability of diazoxide to open these channels. These results provide novel mechanistic links between NO-induced cardioprotection and mitoKATP channels.....";

"Short-term, adenovirus-induced hyperleptinemia depletes adipocyte fat while profoundly down-regulating lipogenic enzymes and their transcription factor, peroxisome proliferator-activated receptor (PPAR)gamma in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPARalpha, normally low in adipocytes, are up-regulated, as are uncoupling proteins 1 and 2. This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor alpha, and leptin, and by the appearance of the preadipocyte marker Pref-1.....";

"PPAR-gamma activators inhibit expression of VCAM-1 and ICAM-1 in activated endothelial cells and significantly reduce monocyte/macrophage homing to atherosclerotic plaques. These findings suggest that PPAR-gamma activators, currently used in treatment of type 2 diabetes, may have beneficial effects in modulating inflammatory responses in atherosclerosis.....";

"RNA derived from adipose tissue of obese humans has increased expression of PPAR gamma 2 mRNA, as well as an increased ratio of PPAR gamma2/gamma1 splice variants that is proportional to the BMI; a low calorie diet specifically down-regulates the expression of PPAR gamma2 mRNA in adipose tissue of obese humans.....";

"Perturbed handling of postprandial triglycerides in normolipidemic CAD patients involves the accumulation of apo C-I–rich large VLDL particles and the generation of small, apo C-I– and cholesterol-rich VLDL remnants.....";

"Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women.....";

"Hepatocyte Growth Factor Overexpression in the Islet of Transgenic Mice Increases Beta Cell Proliferation, Enhances Islet Mass, and Induces Mild Hypoglycemia.....";

"The 4G allele of a 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with increased transcription of the PAI-1 protein, which may lead to decreased fibrinolysis and has even been proposed as a candidate risk factor for myocardial infarction or stroke, BUT the PAI-1 4G/5G genotype was not only NOT associated with risk of myocardial infarction or other cardiovascular mortality, the PAI-1 4G4G homozygotes had a markedly reduced risk of cerebrovascular mortality compared with the 5G5G homozygote....";

"Physiologic elevation in the local plasma insulin concentration increases coronary blood flow in the absence of any increase in myocardial oxygen demand or consumption, suggesting a primary reduction in coronary tone, while simultaneously restraining the oxidation of imported substrates. These observations are consistent with insulin-mediated elaboration of vasoactive and/or paracrine factors within the coronary circulation.....";

"Hemoglobin A1c (of 8.5%) has threshold effect on risk of proteinuria in diabetics.....";

"The Homeodomain of PDX-1 Mediates Multiple Protein-Protein Interactions in the Formation of a Transcriptional Activation Complex on the Insulin Promoter.....";

"Fasting Insulinemia Appears to Associate with Measures of BOTH Increased (t-PA antigen) AND Decreased (PAI-1 antigen) Fibrinolytic Potential.....";

"Results suggest that mito K-atp channels are downstream of PKC in the mechanism of infarct-size limitation by A1-receptor activation and that the anti-infarct tolerance afforded by opening of mito K-atp channels is associated with preservation of mitochondrial function during ischemia/reperfusion.....";

"CD44-positive inflammatory cells may be a potential therapeutic target in [NOD mouse model of] insulin-dependent diabetes.....";

"Diabetic subjects have significantly (P<0.001) more increased Dicarboxylic Acid (DA) excretion in urine than corresponding healthy subjects. The yields of DA's in each group decreased in the order adipic>suberic>sebacic acid. Being stable and easily detectable compounds, DA's may be considered potential markers of oxidative attack on PUFA in diabetes.....";

"Data suggest that LDL particle size should probably be added to the cluster of risk factors that characterize the insulin resistance syndrome. The association of 'insulin resistance' and LDL particle diameter, however, is not mediated directly through the level of insulinemia but via alterations in lipid metabolism.....";

"Still more participants needed for nationwide study to Prevent Type 1 Diabetes.....";

"Guava fruit may benefit type 2 diabetics.....";

"Dominant negative mutations in human PPAR-gamma are associated with severe insulin resistance, diabetes mellitus and hypertension.....";

"The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.....";

"Long-Acting GLP-I agonist Exendin-4 Stimulates Both beta-Cell Replication and Neogenesis, Resulting in Increased beta-Cell Mass and Improved Glucose Tolerance in Diabetic Rats....";

"Glucagon-Like Peptide 1 and Exendin-4 Convert Pancreatic AR42J Cells Into Glucagon- and Insulin-Producing Cells.....";

"New Sweetener (d-tagatose) Also Blunts PostPrandial Hyperglycemia in UMd Study.....";

"In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing.....";

"Results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels (above 6.0 mmol/L [above 110 mg/dL]) or DM and known CHD.....";

"UK GOVERNMENT: Key milestone in the setting of national standards for care of people with diabetes. Health Minister Lord Hunt welcomed members on 10 Dec 1999 to the first meeting of the expert group which will shape new national standards for the care of people with diabetes and reduce unacceptable variations in treatment and care.....";

"Peroxisome Proliferator–Activated Receptor Gene Locus Is Related to Body Mass Index and Lipid Values in Healthy Nonobese Subjects.....";

"A Common Mutation of the Insulin Receptor Substrate-1 Gene Is A Risk Factor for Coronary Artery Disease.....";

"Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.....";

"Coronary Disease in Type 1's Correlates with Depression, NOT Blood Glucose. Lower Extremity Arterial Disease, however, Does Correlate with Blood Glucose in Type 1's.....";

"Genetic Abnormality in Diabetic Mice May Answer Why Autoimmune Disease Are More Common in Women.....";

"Lipid-lowering therapy generally should be more aggressively applied to patients with diabetes and/or at the time of coronary heart disease (CHD) diagnosis.....";

"Uncontrolled diabetes linked to gum disease.....";

"National Survey Reveals Few Type 2 Diabetic Patients Understand Underlying Cause of Their Disease.....";

"Presence of more severe retinopathy or visual impairment in diabetic patients is a significant indicator for increased risk of ischemic heart disease death. Presence of these ocular conditions may identify individuals who should be under care for cardiovascular disease.....";

"Results demonstrate close agreement between GlucoWatch biographer readings and blood glucose measurements using repeated fingerstick blood samples. The automatic, frequent, and noninvasive measurements obtained with the biographer apparently provides more information about glucose levels than the current standard of care.....";

"LDL size is not a predictor of CHD events in elderly white subjects after controlling for diabetes status.....";

"*Vasopeptidase inhibitors* - a new, experimental class of drugs inhibiting both ACE and neutral endopeptidase - appear to be the most potent ever at reducing both systolic as well as diastolic high blood pressure.....";

"Although black subjects experienced higher age- and diabetes mellitus adjusted rates of amputation than their white counterparts, a combination of social and environmental factors may account for the apparent ethnic difference.....";

"High-protein diets do increase individual nephron filtration rate (INFR) and affect glomeruli adversely (1) directly with individual nephron filtration rate increase and (2) inversely with total glomerular filtration rate (GFR) diminution (thus the effect is small in normal functioning kidneys and large in renal impairment).....";

"Diabetes (1) predicts and (2) correlates with index of *In-Stent Restenosis*.....";

"GLP-1 was able to normalize plasma glucose in all type 2-diabetic patients studied thus far........";

"Fiber consumption predicts (fasting *and postprandial*) insulin levels, weight gain, and other CVD risk factors more strongly than total or saturated fat consumption. .....";

"DKA can occur in patients classified as *type 2* [based on previous insulin Rx or subsequent lack of insulin Rx.] Hispanics were mainly *type 2* (47%), with 34% *type 1* and 19% *unknown*. Whites were predominantly *type 1* (80%), with 17% *type 2* and 3% *unknown*. African Americans showed a slight preponderance of *type 1* (53%), with a large number of *type 2* patients (44%) and 3% *unknown*.....";

"Obesity continues to increase rapidly in the United States. To alter this trend, strategies and programs for weight maintenance as well as weight reduction must become a higher public health priority.....";

"Data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes, including physical activity of moderate intensity and duration.[JAMA. 1999;282:1433-1439].....";

"Children and young adults with insulin dependent diabetes continue to be at increased risk for death from diabetic ketoacidosis.....";

"MCV group is now the second to have transfected the insulin gene into hepatocytes.....";

"Gender Difference in Postprandial Lipemia:- Importance of Visceral Adipose Tissue Accumulation..........";

"Eicosapentaenoic Acid and Docosahexaenoic Acid Block Serotonin-Induced Smooth Muscle Cell Proliferation..........";

"Fish Oils Safe and Effective in Angiographic Placebo-Controlled Trials of Coronary Artery Regression and in MI Survival............";

"Low-Cholesterol and High-Fat Diets Reduce Atherosclerotic Lesion Development in ApoE-Knockout Mice..........";

"Type 2 Diabetes in whites, but not blacks, is inversely associated with serum magnesium levels................";

"Orally administered amidated pectin insulin (PI) hydrogel beads sustain plasma concentrations of insulin in streptozotocin (STZ) diabetic rats..............";

"BMI correlates with increased mortality in non-smoking Caucasian Americans (but not in non-smoking black Americans)..........";

"Treatment with ramipril, an ACE inhibitor, can significantly reduce the risk of heart attack, stroke, cardiovascular death and kidney disease in high-risk people with diabetes...........";

"Beta Cell Failure Gets Almost All Type 2 Diabetics In Time.............";

"An isoflavone dietary supplement, P-081, derived from red clover, significantly increases HDL cholesterol levels in postmenopausal women not taking estrogen Rx.........";

"Compared with placebo, long-term use of cilostazol, 100 mg or 50 mg, twice a day significantly improves walking distances in patients with intermittent claudication........";

"Glycemic control is subject to intervention. Better control may decrease hospitalization among people with diabetes. Thus, there is considerable potential for reducing health care costs.........";

"Plasma Leptin Associated with Insulin-Resistant Hypertension............";

"*Nonfasting* Serum Glucose and Insulin Concentrations Significantly Increases the Risk of Stroke..........";

"The agouti gene product stimulates pancreatic -cell Ca2+ signaling and insulin release..........";

"Diabetes common (3x-increased) in hospitalized bipolar patients............";

"Proteinuria Is an Independent Risk Factor for Ischemic Stroke in Non–Insulin-Dependent Diabetes Mellitus.............";

"*Legs for Life* offers free vascular screenings for PVD (peripheral vascular disease) nationwide this month..........";

"Poor diabetic perioperative glycemic control is a risk factor for infectious complications...........";

"Bristol-Myers Squibb warned about Glucophage adverse event reporting.............";

"Jacuzzis may *help control [type 2] diabetes*..........";

"Silent Myocardial Ischemia with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CHD............";

"The greatest cost savings in diabetes care is to be had from reducing cardiovascular complications............";

"Gabapentin not superior to amitriptylline in small, under-powered, cross-over study of pain relief in 28 diabetic neuropathic patients.............";

"HDL's from poorly controlled diabetics are abnormal and do not inhibit LDL-oxidation or Apo-A1 fragmentation in vitro............";

"Even though *secondarily* associating with increased cardiovascular disease in the elderly, higher fasting plasma insulin appears to correlate with *improved survival* in that population............";

"Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity.................";

"The Human ENSA Gene That Encodes alpha-Endosulfine, a Regulator of beta-Cell KATP Channels, has been localized to an area of Chromosome 14 with IDDM susceptibility-linkage (IDDM11)..............";

"C-Reactive Protein is Strongly-Associated With Measures of Obesity, Insulin Resistance, and Subclinical Atherosclerosis in Healthy, Middle-Aged Women...........";

"Insulin resistance in Sicilians has been linked to the PC-1 region of Chromosome 6 [but in Mexican-Americans it has been variously linked to Chromosomes 2,6,10,15,the SUR-1 receptor, and TRP64ARG beta 3AR]..........";

"The allele frequency of the PPAR gamma 2 missense mutation Pro12Ala variant is 0.12 in Caucasian Americans, 0.10 in Mexican Americans, 0.08 in Samoans, 0.03 in African Americans, 0.02 in Nauruans, and 0.01 in Chinese.........";

"The American Heart Association has conceded - *Diabetes is now recognized as a major risk factor for coronary heart disease*...........";

"Low levels of leptin seem to reverse diabetes in mouse model of congenital lipodystrophy...........";

"Stents help diabetic patients who require coronary revascularization..........";

"Melanocyte Stimulating Hormone appears to have appetite-suppressant activity.............";

"An insulin peptide fragment has been identified as an autoantigen in the NOD [Non-Obese Diabetic] mouse model..........";

"Data suggest that persons with type 1 diabetes may not judge correctly when their BG level is too low to permit safe driving and may consider driving with a low BG level even when they are aware of the low level.";

"Health care professionals should counsel their patients about the risk of driving with hypoglycemia and the importance of measuring BG level before driving.............";

"Should we recognize another class of diabetes called *Prandial Diabetes* with different risk factors? Why? The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly...............";

"Postprandial hypertriglyceridemia - [NOT particle size] - along with Proinsulin - [NOT insulin] - and LDL-cholesterol -[NOT small-dense LDL] - found to correlate with atherosclerosis.............";

"Diabetes-Related Lower-Extremity Amputations Disproportionately Affect Blacks and Mexican Americans.............";

"Early renal function decline is 3 times more likely to develop in blacks than whites and potentially modifiable factors, including lower socioeconomic status, suboptimal health behaviors, and suboptimal control of glucose level and blood pressure, account for more than 80% of this disparity.........";

"Gemfibrozil lowers CHD events but again fails to affect total mortality [this time in CHD patients with low HDL and even despite an expected high total mortality from CHD in this population...............";

"NHLBI Investigators Identify HDL (*Good Cholesterol*) Gene................";

"Protein-Rich Diets May Reduce Heart Disease Risk............";

"IL-13 reduces incidence of Type 1 diabetes in NOD mice...........";

"IGT correlates with increased CHD, CHD-related, AND total mortality in Japanese-Americans..............";

"FDA foolishly rejects important new antibiotic................";

"Alcohol use inversely associated with coronary mortality in older onset diabetics............";

"Actos (pioglitazone) approval in Type 2s as monotherapy or in combination with metformin, insulin, or SFU's cautioned by edema, weight gain, and anemia but heartened by lowering triglycerides.................";

"The Insulin Gene has successfully been transfected into diabetic rat livers and significantly improves glycemia..............";

"Watch Sensor Apparently Effective in Monitoring Blood Sugars Non-Invasively Recommended for Approval..........";

"Hypertension in Pima Diabetics Correlates with Renal Disease and NOT with Cardiovascular Disease............";

"Stress Worsens Diabetic Control and Treatment of Depression Improves Diabetic Control............";

"Ultralong-acting Insulin (Glargine) Safer but as Effective as NPH in Types 1 and 2 diabetics........";

"Inhibitor of Diabetic Proliferative Retinopathy Unmasked............";

"Low Carb, High Fat Diet Appears to Improve Major Risk Factors in Type 2 Diabetes.............";

"The Western-Diet Results in Insulin-Resistance, but not Atherosclerosis in LDL-Receptor Deficient Mice with Hypercholesterolemia (But high fructose diets do result in increased atherosclerosis in the same model)................";

"Intensive Insulin Therapy Saves Lives in Acute MI's (The DIGAMI Study)....................";

"Aggressive Cholesterol Lowering after CABG Shows Angiographic Benefit but FAILS to show a Significant Clinical Benefit in Diabetics...........";

"Type 2 diabetics will eventually require insulin for good control.........";

"Nitrendipine Improves Diabetic Mortality in the Elderly with Systolic Hypertension..............";

"Conservative Therapy WITHOUT AMPUTATION Safe and Effective for Diabetic Foot Ulcers and Osteomyelitis.............";

"Reo-Pro and dose TPA are as effective as angioplasties in acute myocardial infarctions..............";

"EAS Study rates Lipitor More Effective Than Zocor or Baycol in reaching target goals............";

"Avandia (Rosiglitazone) approval by FDA cautioned by LDL increase, edema, anemia, and weight-gain.............";

"Parent-Teen Integration into the Diabetic Team Affects Outcomes Positively...........";

"Basal-Bolus (Ultralente/Regular) Insulin Regimen Highly Effective with Carbohydrate Counting in Type 1 Diabetes............";

"Could Type 2 Diabetes be an inflammatory disease? (Adipocyte IL-6 correlates with BMI, insulin resistance,endothelial dysfunction, TNF-alpha, AND CRP)..........";

"Homocysteine a significant risk factor for atherosclerosis post-menopause..........";

"Effects of exercise on decreasing atherosclerosis may be due to inhibition of cytokine release................";

"Hopkins Study Shows Overweight Young Males are at Risk for the Development of Type 2 Diabetes...............";

"Oral insulinomimetic found in the African rainforests (shades of *The Medicine Man* - eh?)..........";

"Focus of attack in Type 1 diabetes may be *stiff-man* antigen GAD.........";

"D-chiro-inositol effective in reducing insulin resistance................";

"NDC recommends metformin as first line MONOTHERAPY therapy in the OBESE (BMI>30) type 2 patient but also recommends caution when using metformin in combination with sulfonylurea agents.......";

"How are obesity and Type 2 diabetes related?...........";

"ADA recommends treatment of all diabetics as though they have coronary disease by NCEP II guidelines........";

"ADA recommends admission of all diabetics who are badly out of control.....";

"How do insurance companies stack up for diabetics?...............";

"Foot Surgery in Diabetes Leads to Increased Degenerative Changes.........";

"Supplementation with beta-carotene for an average of 12 years has no effect on the risk of developing type 2 DM.............";

"Use of Reo-Pro with Stents Improves Diabetic Survival..............";



CONCEPTS


Control is good and less expensive....


Obesity, Leptin, K-ATP Channels and Type 2 Diabetes....
Obesity => Leptin
Obesity => Leptin => "U-shaped" Insulin Resistance Curve
Obesity => Leptin=>Downregulated PPAR-
gamma
=>Enhanced Lipolysis and Decreased Lipogenesispeptide-Y =>
=> Increases in (3) melanocortin function and (4) satiety

Obesity => Leptin => Decreased Insulin Secretion via Opening K-ATP Channels
Sulfonylureas - which prototypically close K-ATP channels - may also increase Leptin
Thiazolidinediones impact Leptin, PPAR-
gamma
, and K-ATP Channels
Mitochondrial K-ATP Channels and Cardiac Ischemia



Mitochondrial Membranes , Mg++, Malate/Oxaloacetate Translocators, Gluconeogenesis, and, Ketoacidosis....


Inflammation, and Type 2 Diabetes....



Postprandial Metabolism and Atherosclerosis Risk....



High Carbohydrate Diets and Atherosclerosis Risk....



Therapeutic Interventions into Diabetic Atherosclerosis....



Therapy of Type 2 Diabetes....



Etiology of Type 1 Diabetes...and the IL-4 Pathway....


Therapy of Type 1 Diabetes....


Diabetic Monitoring and Microvascular Complications (and Atherosclerosis?....)


Type 1 Diabetes

Type 2 Diabetes

Microvascular Complications

*Atherogenesis

Monitoring

Monitoring

General

General

Patho

Nutrition

Nephropathy

Patho

Rx

Patho

Neuropathy

Rx

 

Rx

Retinopathy

 

 


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