Diabetes Mellitus
Diabetes is a disease of inappropriate sugar metabolism. It is commonly divided into two distinct states:
Childhood versus adult onset. Childhood onset otherwise known as type 1 diabetes is an autoimmune
disease with destruction of the islet cells in the pancreas that are mainly responsible for secreting insulin. In
the absence of endogenous insulin production injections of insulin are required to control blood sugar. Oral
medications normally used in type 2 diabetes have very little effect in patients with type 1 diabetes.
Type 2 diabetes is a disease that frequently affects obese patients. The obesity in itself causes the body to
have reduced sensitivity to the effects of insulin. As a result, for many years pre-diabetic patients have to
secrete extra insulin in order to keep blood sugar levels in normal ranges. After years of secreting extra
insulin pancreas finally succumbs to the pressure and can no longer keep up with the demands of a diet
high in sugar and a body that does not respond to insulin normally. Once the discrepancy between the
need for insulin and the ability of the pancreas to meet these demands reach a critical point blood sugar
averaged climb into the abnormal range and pre-diabetics become type 2 diabetics.
Clearly, the picture painted above does not accurately define every patient with type 2 diabetes. Type 3
diabetes is adult onset diabetes that develops in those who are at or close to ideal body weight. Although
the pathophysiology of type 3 diabetes is not clearly defined it is likely a consequence of elemental
imbalances that render cells less sensitive to the effects of insulin independent of body weight. Although the
exact culprits have not yet been definitively defined the candidate culprits include chromium, chromodulin (a
conglomerate of peptides and chromium) intracellular magnesium and vanadium deficiencies or surplus of
calcium.
Evaluation
Pre-diabetes: First signs of diabetes can be detected on routine blood tests. Random non-fasting blood
sugars above normal range (70-120 dependingon the lab performing the test), elevated triglycerides on
fasting lipid panel, elevated fasting insulin levels are early indicators of diabetes. Additionally, certain skin
findings such as development of skin tags or specifically thickening, velvety darkening in the axilla, base of
the neck, under the breasts and knuckles are hallmarks of insulin resistance.
Laboratory Testing:
Glucose tolerance test: This test evaluates response to a standard solution of glucose, roughly equivalent
of one can of soda. Levels above 140 2 hours after the challenge are diagnostic for diabetes.
Glucose tolerance can be further completed by evaluating C-peptide levels. In pre-diabetics glucose levels
may remain in normal range 2 hours after the challenge with the standard sugar solution. However, this has
to be accomplished by much higher levels of insulin than in normal subjects. As such, the development of
diabetes can be accurately forecasted by measuring insulin levels at the 1/2, 1 and 2 hour time points.
Hemoglobin A1C (Hgb A1C): This is a measure of glucose deposition on the red blood cell protein,
hemoglobin. Since the average red blood cell has a life span of 3 months, measuring deposited sugar on
hemoglobin reflects a 3 month average of serum glucose levels. Hgb A1C levels above 6 are considered
diagnostic for diabetes. For diabetics taking medications that cause increase insulin secretion or are on
insulin therapy a Hgb A1C goal of 7 is ideal. For those on therapy with medications that increase insulin
sensitivity or otherwise do not predispose to low blood sugars a Hgb A1C goal of 6 is desirable.
C-peptide: C-peptide is a measure of endogenous insulin levels. Fasting C-peptide levels can serve as a
short term indication of insulin resistance. Elevated fasting C-peptide levels can serve as an early indication
of pre-diabetes. Additionally, it can serve as a short term measure of efficacy of any given therapy for
diabetes.
4 Hour Urinary C-Peptide
http://www.ncbi.nlm.nih.gov/pubmed/6400710following standard 600 kcal challenge
Glycomark: This test available since 2008 measures blood levels of 1,5-anhydroglucitol (1,2-AG). This
substance is a sugar similar in structure to glucose. Levels of 1,5-AG are constant in those with normal
sugar metabolism. This is in large part due to the fact that with normal serum glucose levels and normal
kidneys regulate blood levels of 1,2-AG within a tight “normal” range. When blood levels of glucose climb
above 180, glucose interferes with the reabsorption of 1,2-AG. his leads to lowering of serum levels of 1,2-
AG. Thus lower levels of 1,2-AG are indicative of high postprandial levels of serum glucose over the
previous 1-2 weeks.
In addition to C-peptide levels, Glycomark is a good indicator of short term blood sugar control.
Furthermore, 40% of all diabetics with good control defined as Hgb A1C goal of 7 will have elevated
postprandial blood sugars. Using Hgb A1C alone will miss the elevated postprandial levels that likely
contribute to higher triglyceride levels and other metabolic complications that lead to complications of
diabetes such as heart attacks. Persistently low glycomark levels indicate higher postprandial blood sugars.
It may indicate the need for specific medication to treat postprandial blood sugars such as Januvia, Byetta
and Symlin. Glycomark.com
Therapy
Therapy of all 3 types of diabetes are to prevent complications of disease. Direct problems arising from
poor sugar control include diabetic ketoacidosis in type 1 and hyperglycemic coma in type 2 and 3. Both
sets of complications require expert care in the intensive care unit and are both potentially immediately life
threatening.
Long term complications of diabetes are classified as macrovascular (large vessel) including coronary and
cerebrovascular complications (heart attacks, strokes and peripheral vascular disease). Microvascular
(small vessel) complications include retinopathy, nephropathy and neuropathy. It is estimated that with
every 1% decline in Hgb A1c is associated with a 14% decline in heart attacks in diabetics. Furthermore,
lowering the Hgb A1C from 9 to 7.2% will lead to reduction in cardiovascular complications by 41%,
neuropathy by 60%, retinopathy by 63% and nephropathy by 54%.
Treatment of type 1 diabetes is accomplished by insulin therapy. This is commonly accomplished by using
regular insulin in a pump that delivers insulin subcutaneously at a preset rate. This is often accompanied by
boluses of insulin along with meals to help the body manage the sudden rise in serum glucose levels that
accompany meals and snacks. Another option is to use a once day preparation of insulin such as Lantus.
This must be combined with use of regular insulin before meals.
Many options exist for the treatment of type 2 diabetes. Sulfonylureas, medications that increase insulin
secretion from the pancreas are the oldest class of medications used in the treatment of type 2 diabetes.
They include medications such as glucatrol, glipizide, amaryl and various other brand names. These
medications are effective and have long term safety records. However, they do not alter the underlying
problem and in fact rely on the functioning of an already stressed pancreas to produce more insulin. As a
result these medications are quickly falling out of favor in the therapy of type 2 diabetes.
Currently, guidelines for treatment of type 2 diabetes starts with use of Metformin, dietary modification and
potentially supplementation with magnesium and chromium all as first line therapies for newly diagnosed
diabetics. Additionally, the same regimen can be used in patients identified as either pre-diabetic or with
certain other conditions such as polycystic ovarian syndrome that predispose patients to developing
diabetes down the line.