January 30, 2013

Is It Possible?

Every now and then I get to wondering about the different types of diabetes and if there is more to the diagnosis than the medical community is acknowledging. With the new guidelines from the American Diabetes Association which can be read here (and I urge you to take time to read this), I often read this more carefully than any other provision or discussion in the guidelines. Then I start to look for what they may not be telling us. In any of the discussions, they seem to like to paraphrase some areas by saying that there is much to be determined at the clinical level.

The definition by its very nature leaves many questions, “Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.”

I am using only the first part of the long definition because I think this is where some defining needs to be done. Yes, I agree that diabetes is a metabolic disease and maybe a group. Why the term hyperglycemia is not defined as being a certain measurable amount or number leaves me wondering what they are looking for in not defining this. Certainly they have a number in mind. Then they use chronic hyperglycemia to define what may happen to certain organs. I can understand why some organs are missing from the list because of the lack of conclusive studies for hearing and cognitive decline (brain). I do question why they are not given any mention and a statement of lack of conclusive evidence. That could then spark studies to prove that. I suspect they are not mentioned to avoid these studies from taking place, but why?

The classification for the last several years has gotten more restricted and only includes four classifications. Table one below shows the four classes.
Table 1 Etiologic classification of diabetes mellitus:
1. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency)
1. Immune mediated
2. Idiopathic
2. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)
3. Other specific types
1. Genetic defects of β-cell function
1. MODY 3 (Chromosome 12, HNF-1α)
2. MODY 1 (Chromosome 20, HNF-4α)
3. MODY 2 (Chromosome 7, glucokinase)
4. Other very rare forms of MODY (e.g., MODY 4: Chromosome 13, insulin promoter factor-1; MODY 6: Chromosome 2, NeuroD1; MODY 7: Chromosome 9, carboxyl ester lipase)
5. Transient neonatal diabetes (most commonly ZAC/HYAMI imprinting defect on 6q24)
6. Permanent neonatal diabetes (most commonly KCNJ11 gene encoding Kir6.2 subunit of β-cell KATP channel)
7. Mitochondrial DNA
8. Others
2. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall syndrome
4. Lipoatrophic diabetes
5. Others
3. Diseases of the exocrine pancreas
1. Pancreatitis
2. Trauma/pancreatectomy
3. Neoplasia
4. Cystic fibrosis
5. Hemochromatosis
6. Fibrocalculous pancreatopathy
7. Others
4. Endocrinopathies
1. Acromegaly
2. Cushing's syndrome
3. Glucagonoma
4. Pheochromocytoma
5. Hyperthyroidism
6. Somatostatinoma
7. Aldosteronoma
8. Others
5. Drug or chemical induced
1. Vacor
2. Pentamidine
3. Nicotinic acid
4. Glucocorticoids
5. Thyroid hormone
6. Diazoxide
7. β-Adrenergic agonists
8. Thiazides
9. Dilantin
10. γ-Interferon
11. Others
6. Infections
1. Congenital rubella
2. Cytomegalovirus
3. Others
7. Uncommon forms of immune-mediated diabetes
1. “Stiff-man” syndrome
2. Anti-insulin receptor antibodies
3. Others
8. Other genetic syndromes sometimes associated with diabetes
1. Down syndrome
2. Klinefelter syndrome
3. Turner syndrome
4. Wolfram syndrome
5. Friedreich ataxia
6. Huntington chorea
7. Laurence-Moon-Biedl syndrome
8. Myotonic dystrophy
9. Porphyria
10. Prader-Willi syndrome
11. Others
             4. Gestational diabetes mellitus
The third item seems to be the catchall for everything not fitting into the other three classifications. Notice that for all the things listed, prediabetes is not among them. This is only considered a risk for type 2 diabetes and nothing more. “In 1997 and 2003, the Expert Committee on Diagnosis and Classification of Diabetes Mellitus recognized an intermediate group of individuals whose glucose levels do not meet criteria for diabetes, yet are higher than those considered normal.”

They then define the blood glucose impairment range as “having impaired fasting glucose (IFG) [fasting plasma glucose (FPG) levels 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)], or impaired glucose tolerance (IGT) [2-h values in the oral glucose tolerance test (OGTT) of 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)].” Then they state that these have been referred to as having prediabetes, but do not go on to use any other term. This is the only use of the word.  They only use the term individuals to describe these people with A1cs of 5.7% to 6.4%. They emphasize that they are to be informed of their risks for diabetes and cardiovascular disease. Like all good doctors, they want them counseled about effective strategies to lower their risks.

So what is purpose of the Expert Committee on Diagnosis and Classification of Diabetes Mellitus?  Is this the end of the use of the term prediabetes and how soon can we expect another term?  All good questions we will have to wait for an answer.  Is it possible we may have another term or will diabetes be expanded to include this range?  Even this discussion on prevention or delay of diabetes only uses the term prediabetes once.  Or will it take another decade or more to make the change?

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