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The conundrum of good diabetes care
Submit responseDear Editor,
The comprehensive review shows that the use of glycated hemoglobin as a sole guide for the type 2 diabetes management is not ideal (1). This may be in part due to the circumstance that down-stream glucose metabolites are also harmful.
Methylglyoxal is formed as a glucose metabolite in the cells and, as a bicarboxylic compound, it can crosslink protein species (2). Thus, increased glucose entry in cells can increase the methylglyoxal concentration.
It seems also to downregulate signaling cascades. For instance, the Raf-1, a protein thr/ser kinase is downplayed (3).
Methylglyoxal is metabolized to D-lactic acid which can be used as its versatile biological marker (4).
References
1. Montori VV, Fernandez-Balsells M. Glycemic control in type 2 diabetes. Time for evidence-based about-face. Ann Intern Med 2009; 150: 803
2. Chellan P, Nagarajah RH. Protein crosslinking by the Maillard reaction. Dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys 1999; 368: 98
3. Du J, Zen J, Ou X, et al. Methylglyoxal downregulates Raf-1 protein through a ubiquination-mediated mechanism. Int J Biochem Cell Biol 2006; 38: 1084
4. Talasniemi JP, Pennanen S, Savolainen H, et al. Assay of D-lactate in diabetic plasma and urine. Clin Biochem 2008; 41: 1099
Conflict of Interest:
None declared
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Complicated?
Submit responseSo much theory, so much data, so little time. Is the care of patients with Type 2 DM complicated?
It actually seems fairly straightforward unless we have a hard time giving up our past biases that "lower is always better".
The patients I meet generally are overwhelmed with testing, clinic visits, finger sticks, and bills. Many welcome the good news that they are doing well and seem relieved and comforted that they needn't titrate their A1c to goals not supported by the 3 large recent trials. They can enjoy the life that has been prolonged by fairly simple things like exercise, reasonable diet, and a patient-driven set of goals.
Conflict of Interest:
None declared
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Glycemic Control, Drugs, Goals, and Pulse Mass Index in T2 Diabetes
Submit responseGlycemic Control, Drugs, Goals, and Pulse Mass Index in T2 Diabetes
When trying to balance the pros and cons of the concept of tight glycemic control, it is not so obvious or intuitive to conciliate the real world of evidence and clinical results, with the theory.
In fact, a control of GlycoHbA1c around 7% is very reasonable, as long the main 7 Goals in T2 Diabetes and Cardiovascular Prevention are also controlled.
Those are: 1.- Diet/Nutrition/Education, 2.- Exercise, 3.- No smoking, 4.- Glycemic control, 5.- Blood Pressure control, 6.- Lipids control, 7.- Aspirin when appropriate.
In their original Editorial comparing the trials ACCORD versus ADVANCE (1), Dluhy and Mc Mahon pointed to the fact that in ACCORD there were significantly more deaths and adverse effects like severe hypoglycemia and weight gain than in ADVANCE.
The use of insulin and glitazones was also much more intense, which helps to explain hypoglycemia (usually accompanied by adrenergic reactions like tachycardia) and weight gain. Both drugs have been recently associated with more cardiovascular adverse effects (2, 3).
I consider that the increased risk can be explained by an increase in the Pulse Mass Index (Resting Heart Rate by Body Mass Index divided by 1730, ideal under 1.0), which I reported years ago to correlate strongly with the global cardiovascular risk calculated by the Framingham Risk Score (4).
Drugs like metformin (as also the gliptines), in opposition to insulin and glitazones do not provoke weight gain or hypoglycemia, nor increase the Pulse Mass Index, and metformin is well known to reduce mortality and cardiovascular complications.
Drugs that reduce or not increase the Pulse Mass Index, like Beta blockers or diuretics, tend to improve the long term cardiovascular prognosis, contrary to potent rapid acting vasodilators that increase pulse rate, retain water and do not reduce mortality.
The effects of used and studied anti-diabetic and cardiovascular drugs on the Pulse Mass Index should be carefully observed, as also the concept and consequences of tight glycemic control.
References:
1. Dluhy RG and McMahon GT. Intensive Glycemic Control in the ACCORD and ADVANCE Trials. N Engl J Med. 2008;358:2630-2633
2. Mellbin LG et. al. The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial. European Heart Journal.2008;29(2):166-176
3.-Choy CK et. al. Type 2 diabetes mellitus and heart failure. Pharmacotherapy. 2008 Feb;28(2):170-92.
4. Sanchez-Delgado E. and Liechti H. Lifetime risk of developing coronary heart disease. Lancet 1999;353:924-925 Competing interests: None declared
Conflict of Interest:
None declared