The ABCs of Diabetes Mellitus

1. What is Diabetes Mellitus: Insulin deficiency; Hyperglycemia; Chronic Complications

2. Classification: Type 1 diabetes (B-cell destruction, usually leading to absolute insulin deficiency); Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance); Other specific types (genetic defects of B-cell function, genetic defects in insulin action, diseases of the exocrine pancreas, endocrinopathies, drug or chemical induced, infections, uncommon forms of immune-mediated diabetes, other genetic syndromes sometimes associated with diabetes); Gestational diabetes mellitus

3. Diagnosis

1. HbA1c = or >6.5%.  The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.*
2. FPG= or >126 mg/dl (7.0 mmol/l).  Fasting is defined as no caloric intake for at least 8 h.*
3. 2-h plasma glucose = or >200 mg/dl (11.1 mmol/l) during an OGTT.  The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose = or > 200 mg/dl (11.1 mmol/l).

*In the absence of unequivocal hyperglycemia, criteria A-C should be confirmed by repeat testing.

4. Initial Presentation

1. Type 1 diabetes
2. Type 2 diabetes

5. Initial Management

1. Type 1 diabetes
2. Type 2 diabetes

6. Ongoing Management

1. General Principles/Care goals: Best outcomes with comprehensive, well-organized, patient-centered approach; General care goals: HbA1c <7%; LDL-cholesterol <100 mg/dl; blood pressure <130/80

7. Monitoring for Complications/Associated Disorders

Retinopathy

Nephropathy

Neuropathy

Cardiovascular diseases

Autoimmune disorders (in patients with type 1 diabetes): thyroiditis, pernicious                            anemia, celiac disease

8. Screening for Diabetes?

9. The Future?

References:

1. American Diabetes Association (ADA) Clinical Practice Recommendations.  On an annual basis, the ADA publishes diabetes care recommendations in the journal Diabetes Care (www.diabetes.org/diabetescare).  This very useful resource is updated every January.
2. www.endodoc.org.  This is my medical blog and it contains quite a number of entries on various aspects of diabetes care as well as other endocrine and health care topics.
3. Gwande A: The bell curve.  What happens when patients find out how good their doctors really are?  The New Yorker, December 6, 2004, p 82-91 (www.newyorker.com/archive/2004/12/06/04).
4. Ishani A et al: Effect of nurse case management compared with usual care in controlling cardiovascular risk factors in patients with diabetes: a randomized controlled trial.  Diabetes Care 2011;34:1689-94
5. Hu Y et al: Short-term intensive therapy in newly diagnosed type 2 diabetes patients partially restores both insulin sensitivity and B-cell function in subjects with long-term remission. Diabetes Care 2011;34:1848-53
6. Fajans SS, Bell GI: MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878-84.
7. Nathan DM et. al.: Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy.  Diabetes Care 2008;31:1-11.
8. The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD): Effects of Intensive Glucose Lowering in Type 2 Diabetes.  N Engl J Med 2008;358:2545-59.
9. The ADVANCE Collaborative Group:  Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes.  N Engl J Med 2008;358:2560-72.
10. Nathan DM, et. al.: Impaired fasting Glucose and Impaired Glucose Tolerance: Implications for Care.  Diabetes Care 2007;30: 753-9.
11. Diabetes Prevention Program Research Group.:  Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin.  N Engl J Med 2002;346:393-403.
12. DCCT Research Group:  The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-term Complications in Insulin-Dependent Diabetes Mellitus.  New Engl J Med 1993;329:977-86.
13. DCCT-EDIC: Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000;342:381-89.
14.  DCCT/EDIC Public Website: slides can be obtained 6 months after publication of data.  http://www.gwu.edu/Edic/.  In addition, Susan Hitt the DCCT/EDIC Study Coordinator (Hitts@health.missouri.edu) can furnish you with a full list of DCCT/EDIC publications, abstracts, and presentations.
15. UKPDS: Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Diabetes Study (UKPDS) Group.  Lancet 1998;352:837-53.
16. UKPDS: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.  Lancet 1998;352:854-65.
17.  National Glycohemoglobin Standardization Program (NGSP) website: http://www.ngsp.org.
18. Goldstein DE et. al.: Tests of Glycemia in Diabetes.  Diabetes Care 2004;27:1761-73.
19. Sacks DNB et. al.: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.  Clin Chem 2002;48:436-72.
20. Nathan DM et. al.: Translating the A1c assay into estimated average glucose values. Diabetes Care 2008;31:1473-8.
21. Gilbert RE, Marsden PA.: Activated Protein C and Diabetic Nephropathy.  N Engl J Med 2008;358:1628-30.
22. Nauck MA et al: Dapagliflozin versus glypizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin.  Diabetes Care 2011; 34:2015-22.
23. Bunck MC et al: Effects of exenatide on measures of B-cell function after 3 years in metformin-treated patients with type 2 diabetes.  Diabetes Care 2011;34:2041-47.
24. DeFronzo RA et al: Pioglitazone for diabetes prevention in impaired glucose tolerance.  N Engl J Med 2011;364:1104-15.

TABLE 1. Medications for Patients with Type 2 Diabetes

Insulin

Medications that stimulate insulin release

1. Sulfonylureas (SURs): Advantages- long-term experience, inexpensive, oral administration; Disadvantages- weight gain, ?increased risks for cardiovascular diseases, hypoglycemia
2. Glinides (e.g., repaglinide, nateglinide): Advantages- shorter-acting than SURs, only occasional hypoglycemia; Disadvantages- expensive, GI side-effects, weight gain

Medications that enhance insulin action

1.  Incretin mimetics (glucagon-like peptide agonists, or GLP-1 agonists such as exenatide): Advantages- weight loss, infrequent hypoglycemia, can be given weekly; Disadvantages- expensive, requires injections, frequent GI side-effects
2. Incretin sustainers (dipeptidyl peptidase-4 inhibitors or DPP4 inhibitors such as sitagliptin): Advantages- oral administration, rare hypoglycemia; Disadvantages- costs, GI side-effects
3. Amylin-like agents (e.g., pramlintide): Advantages- ?weight loss; Disadvantages- hypoglycemia, injections tid, costs
4. Thiazolidinediones or TZDs (e.g., pioglitazone):Advantages- improved lipid profiles, no hypoglycemia, ?prevent/slow loss of insulin secretory capacity; Disadvantages- costs, weight gain, fluid retention and heart failure

Medications that inhibit glucose absorption from the gut or reabsorption from the kidney

1. Alpha-glucosidase inhibitors (e.g., acarbose): Advantages- ?weight loss; Disadvantages- costs, GI side-effects (frequent), tid dosing
2. Sodium-coupled glucose co-transporter (SGLT2) inhibitors (e.g., dapagliflozin): Advantages- rare hypoglycemia, weight loss; Disadvantages- UTIs, polyuria, costs, uncertain risk/benefit ratio

Medications that decrease hepatic glucose production (e.g., metformin): Advantages- no hypoglycemia as monotherapy, inexpensive, oral administration, ?weight loss; Disadvanages- rare lactic acidosis, GI side-effects (generally mild)

The Findings

The investigators found that an authoritative parenting style was associated with better adherence to the treatment plan and lower HBA1c levels than was an authoritarian parenting style.  I had actually never heard the term “authoritative parenting style” before.  This parenting style is characterized by a parent who sets clear limits for the child in a noncoercive way.  This parenting style is to be distinguished from a permissive parenting style and an authoritarian parenting style.  The latter style is characterized by harsh, coercive, and punitive parenting.  The investigators found that only in fathers did the authoritative parenting style reap benefits for the child.  Among the mothers, a permissive parenting style was associated with less well controlled diabetes as was an authoritarian style.  For both mothers and fathers, a sense of helplessness was associated with less well controlled diabetes (for fathers) and poorer adherence to treatment (for mothers).  The investigators concluded that their study results were consistent with previous studies on parenting style in adolescents with diabetes and that more involvement by fathers who exhibit an authoritative style of parenting would be beneficial.

Translation of these research results to patient care?

These data may explain differences in glycemic control among adolescents with diabetes, but can the information be used to actually improve glycemic control in adolescent patients?  That study has yet to be carried out.  For now, it makes good sense to work with mothers and fathers of children with diabetes and strive to promote authoritative parenting styles (as opposed to permissive or authoritarian styles) and in particular, to promote more involvement by fathers in the care of their children and adolescents with diabetes. In closing, I must confess that I have no idea how to teach parents to be authoritative rather than authoritarian or permissive in dealing with their teenagers, nor do I know if it can actually be taught. effectively.  But, it seems to be worthwhile to try.  I wonder what kind of a parent I was to my children when they were teens?  Maybe I don’t want to know?

Is this new and exciting information?

The association between statin use and slightly increased risk of diabetes is not a new observation; last year The Lancet published a study of 90,000 patients taking statins and showed an increased risk of about 9% (the present study included about 32,000 patients).  So, these new data are mostly “same old same old.”  In fact, I am not sure why the study got so much attention by the New York Times, other than many people take statins and article was published in JAMA.  Anyway, the article quoted Dr. Steven Nissen, a cardiologist from the Cleveland Clinic, who said he didn’t think the information was very important. What I found amazing was that neither the author of the newspaper article or any of the people quoted in the article raised the possibility that the study findings really had nothing at all to do with statins causing diabetes.  For example, maybe the association is related to the fact that more people who develop diabetes have lipid abnormalities and are more likely to be treated with statins?  Instead, the article focused on the possible mechanisms by which statins could lead to the development of diabetes.   The only way to answer this question would be to do a long-term randomized clinical trial in which patients with abnormal lipid levels were either treated with statins or just monitored.  I am not suggesting that such a study be carried out since it probably wouldn’t be ethical given the proven  benefits of statins to treat lipid abnormalities and decrease risk for the development of cardiovascular disease.  What I am suggesting is that those who write articles in newspapers and magazines about medical studies, be more careful to make sure readers understand the difference between cause/effect and association.  This was not even considered in this New York Times article.

The second media piece was in the Business section, page 5 of the New York Times, Sunday March 26, 2010.  The piece is entitled “Carrots, Sticks and Lower Premiums” written by Steve Lohr.   The article addresses the mostly unspoken truth that health care reform in the U.S. would benefit in an extraordinary way if all of us lived healthier lives.  Data do show that 50-70% of our nation’s health care costs are preventable, mostly attributable to treatment for chronic complications that mostly related to unhealthy behaviors.  The article is about how employers are beginning to wake up to the fact that it is good business to have healthy employees.  Read the article.

The third piece is an article that appeared the other day in the New England Journal of Medicine (March 25, 2010).  The title of the article was “Prevalence of Diabetes among Men and Women in China” and written by Wenying Yang and colleagues.  The investigators studied whether the rapid change in lifestyle in China has increased diabetes prevalence.  The study population included 46,239 adults, 20 years of age or older, from 14 provinces and municipalities tested between June 2007 and May 2008. The results were astonishing.  China is catching up with the U.S., and I’m not talking about their economy.   The age-standardized prevalences of total diabetes (previously undiagnosed and previously diagnosed diabetes)  were 10.6% in men and 9.7% in women.  For prediabetes (abnormal blood glucose levels but not diagnostic for diabetes), the prevalences were 16.1% in men and 14.9% in women.  The data showed a sharp and steady increase in the national prevalence of diabetes from surveys conducted in 1980, 1994, and 2001 (e.g., prevalence in 1994 was 2.5%).  Not surprisingly , the prevalence was considerably higher in urban residents than among rural residents.  The investigators concluded the following: “that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.”

So?

I don’t think I really need to explain how the 3 media pieces relate to one another.  The prevalence of diabetes in China is now just about the same as the prevalence in the U.S. (prevalence of 9.6% based on the National Health and Nutrition Examination Survey 2003-2006).  It’s the price we now pay globally for our economic advances coupled with our genetic predisposition to obesity and diabetes (check out some of my old entries if you have forgotten).   Jamie Oliver knows what do do about the problem in both the U.S. and China and so do employers trying to get their employees healthier, and so do you.

What Everybody Ought to Know About the Benefits of being fit if You Have Diabetes: Effects of Exercise on Blood Glucose Levels

Written by Sue Rollins

Did you know that you can more easily manage your diabetes just by engaging in regular exercise?  Exercise generally has a very beneficial effect on blood  glucose levels in people with type 2 diabetes. When you engage in exercise, you expend a lot of energy.  This first comes from the glucose stored in your liver and your muscles.  At first, the body simply uses up the stored glucose (in the form of glycogen).   Thus, engaging in exercise does not mean your blood glucose levels will necessarily fall to dangerously low levels.   The situation is somewhat different in people with type 1 diabetes and in people with type 2 diabetes who take medications that can cause hypoglycemia.  Often these people need to take snacks at regular intervals during exercise to avoid hypoglycemia.  The body is very clever and has a number of mechanisms to prevent the blood glucose level from falling too low.  For example, with exercise and also if the blood glucose level drops below normal, glucagon, a hormone stored in the pancreas gets released.  This hormone promotes further release of glucose stored in the liver.  The same is true of the hormone epinephrine, stored in the adrenal cortex.  If one does enough exercise to use up most of the stored glucose, the body can make “new” glucose from the breakdown of proteins.  Also, breakdown of fats will occur, providing an alternative source of  energy, thereby “sparing” glucose stores.  In addition, regular exercise actually increases a person’s insulin sensitivity, making the insulin they produce (or take), more effective in controlling blood glucose levels.

Why is the effect of exercise on glucose levels important to those with type 2 diabetes?

Exercise indeed has a good effect on a patient’s glucose level. This is good news for people who have type 2 diabetes. A lot of research indicates that patients of diabetes gain more control over their diabetes as soon as they get into to a regular exercise program.  Since exercise improves your insulin sensitivity, you may need less medication in order to control the diabetes.

Should patients with type 2 diabetes exercise more often or differently than otherwise healthy people?

Experts recommend that people who have type 2 diabetes should exercise about 30-60 minutes (usually only moderate aerobic activity) at least 3 days a week.   Any amount of exercise is better than no exercise.

What type of exercise is best for patients with type 2 diabetes?

Most experts believe the frequency of the exercise routine is more important that the specific kind of exercise one engages in. Ideally, the exercise program will include aerobic activities and include some weight training.

When should patients be discouraged from exercising?

Some patients have a higher risk of developing injuries from the stress of an intense exercise program. Such patients include those with preexisting diabetes eye disease, hypertension and other cardiovascular risks.  Obviously, those who have been  leading sedentary lifestyles. need to take it slow and easy.  All patients should be thoroughly evaluated by their physicians before beginning a new exercise program.

About the Author – Su Rollins writes for <a
href=”http://www.hypoglycemicdiet.org”>reactive hypoglycemic diet</a> ,
her personal hobby blog focused on tips to prevent and cure hypoglycemia
using the right diet and nutrition.

If you have access to the full article and the editorial comment, I urge you to read them (it will cost you a bundle unless you have access to a medical school library and have privileges to obtain the articles).  In my opinion, the newspaper article did not really convey the gist of the study in a way that was easy to understand.  In reading the newspaper article I got the sense that some major breakthrough had occurred.  When I read the actual scientific report, I was much less impressed that we were on the brink of “the holy grail” as the title of the editorial comment suggested we might be.

What is a closed-loop insulin delivery system?

In people who do not have diabetes, their insulin delivery is within a closed-loop system.  This means that insulin delivery is automatically regulated based on need.  The cells in the pancreas that secrete insulin (the beta cells) are little computers that read the blood glucose level continuously and secrete insulin as needed to maintain  blood glucose levels in the normal range.  It’s the same idea as with a thermostat on the wall.  It reads the ambient temperature continuously and depending on the particular system, can heat or cool the air as needed to maintain the temperature within a very narrow range.  These are closed-loop systems.  In contrast, an open-loop system doesn’t do things automatically to maintain the status quo.  Someone needs to manually “close the loop.”  With respect to room temperature, it would be necessary to check the temperature and manually adjust the temperature up or down as needed. With respect to diabetes, the standard approach uses an open-loop system approach to adjust insulin injection doses or rates of infusion for people who use insulin pumps, based on blood glucose readings and/or anticipated food intake or activity.  Are you with me so far?

How was the study designed?

The investigators studied 19 patients with type 1 diabetes age 5-18 years.  The patients were treated with either standard continuous subcutaneous insulin infusin (OLCSII) or a closed-loop system (CLCSII).  Remember, the OLCSII is an open-loop system in which the patient adjusts the insulin infusion rate and/or the doses with meals based on fingerstick blood glucose testing.  Comparisons were made between OLCSII and CLCSII overnight, after rapidly and slowly absorbed meals, and after exercise.  Patients were masked to both blood glucose and interstitial glucose levels during all 3 protocols; the sensor glucose levels were interstitial glucose readings obtained almost continuously.  Investigators were masked to blood glucose levels but not sensor readings.  During the overnight studies, the sensor glucose readings were fed every 15 minutes to a computer which calculated insulin infusion rates based on an algorithm.  A nurse then “closed the loop” by manually adjusting the insulin infusion rates.  During nights when the patients used OLCSII, the insulin infusion rate was not adjusted based on either fingerstick blood glucose or interstitial glucose readings.  The primary outcome was time during which plasma glucose levels were in the range 70-144 mg/dL or below 71 mg/dL.

What happened?

The results showed no statistically significant differences between OLCSII (21 nights in 17 patients) and CLCSII (33 nights in 17 patients).  Likewise, there were no statisticallysignificant differences between the treatment groups with the meal and exercise protocols.  A secondary analysis of the data in whch the results from the 3 protocols were pooled showed increased time in the target range (60% vs. 40%) for CLCSII and reduced time with glucose levels below the target range (2.1% vs. 4.1%).  These differences were statistically significant.  The investigators reported that “no events” occurred in the CLCSII group when plasma glucose was below the target range, meaning no hypoglycemic symptoms; in the OLCSII group, 9 events were recorded.  The investigators concluded that CLCSII “could reduce the risk of nocturnal hypoglycemia in children and adolescents with diabetes.”

What does it all mean?

First, it was rather surprising to me that this study made such a media “splash” given that the data showed no statistically significant differences between OLCSII and CLCSII for the primary outcomes data analyses.  It was only with the secondary analyses (after the fact so to speak) that statistically significant differences were shown.  Basically, it was only by “data mining” that the investigators showed statistically significant differences between the two arms of the study that favored CLCSII.  What I am trying to say in polite terms is that the data manipulation in the study was not a very good way to show that CLCSII might be better than OLCSII in preventing nocturnal hypoglycemia in children and adolescents using CSII even though CLCSII might really be quite a bit better.  I thought the investigators actually interpreted their data rather conservatively and hinted that CLCSII might just decrease risks of nocturnal hypoglycemia but that further studies were needed.  Mostly, I agree with their conclusions and found the data interesting.  At the same time, I found the New York Times article a bit over the top with its summary of the study and the possible clinical implications.  It’s not for me to say but I wouldn’t have thought a small study with no statistically significant different outcomes for the primary data analyses between “standard care” and and a new approach would have merited a report on the first page of the Business section of the New York Times.  Maybe I have misinterpreted things?  Since the report was placed in the Business section and not the Science section, maybe it’s all about the commerical possibilities of  CLCSII?

What do the data really mean?

I do not want to be viewed as cynical in my criticism of the New York Times report.  Hypoglycemia is a serious matter and anything we can do to decrease diabetic patients’ risks for hypoglycemia should be embraced.  I would agree that the study was a sort of “proof-of-concept” for the use of a continuous glucose monitoring system and a computer to adjust insulin infusion rates to decrease patients’ risks for nocturnal hypoglycemia.  On the other hand, there was no discussion in the medical article or the newspaper article that previous long-term studies with continuous glucose monitoring using interstitial glucose monitoring as in present study has not shown less hypoglycemia (nocturnal or otherwise) in either children or adults with type 1 diabetes and only minimal overall improvement in blood glucose control in adults and none in children (see New Engl J Med 2008;359:1464-76).  In addition, most hypoglycemia in patients with type 1 diabetes, whether they are being treated with CSII or other types of insulin regimens can be prevented by appropriate adjustments in insulin doses based on fingerstick blood glucose testing.  It is just that such adjustments require patients to be highly knowledgeable about their diabetes and compulsively attentive to their self-care.  That’s not so easy.  Maybe while we’re waiting for a cure, it’s a good idea to work hard on temporary fixes such as closed-loop insulin delivery systems?  At the same time we must be very careful to separate hype generated by those commercial interests dreaming of big bucks and scientific truth.  Fear of hypoglycemia must not push us into expensive treatment approaches that are theoretically useful but cannot be shown to be clinically helpful without resorting to secondary data analyses.

So-called national guidelines, consensus statements, and expert opinions should all be viewed with considerable suspicion since they are often put together by many interested parties with very different points of view.  Typically, such treatment guidelines are compromises hammered out among physician experts, insurers, special interest groups and are anything but “consensus statements.”  The problem with consensus statements and treatment guidelines put together by expert groups is that however incorrect they might be, individual physicians who ignore these guidelines when treating their patients run the risk of not having the treatments covered by health insurance or by risks of malpractice lawsuits when results are not satisfactory.  Anyway, I highly recommend that you read the article and I can asure you that my recommendation was not put together by a committee.

The Mauer study design

Mauer and colleagues studied 285 people with type 1 diabetes at least 18 years of age with diabetes duration 2-20 years.  Patients were excluded from the study if they had hypertension or any evidence of diabetic nephropathy.  Most patients had kidney biopsies at the beginning and end of the study which lasted 5 years.  The patients were randomly assigned to one of three treatment groups: placebo, Losartan (an ACE inhibitor) or Enalopril (an ACE inhibitor.

Study results

Basically, the study showed no benefit in terms of development of elevated microalbumin levels with the ACE inhibitors; in fact, the Losartan group actually showed a statistically significant higher incidence of elevated microalbumin levels than did the placebo group.  Among the three  treatment groups, there were no differences in the extent of morphologic kidney changes over the 5-year period.  Both ACE inhibitor groups showed significantly less progression of diabetic retinopathy (65-70% less risk for progression).

So now what?

These results were, to say the least, surprising to many experts.  The question remains how to reconcile the Mauer study results with results of earlier studies and what to do with patients who are now being treated with ACE inhibitors?  In my opinion, we should not panic, but sit back and try to sort this all out.  There are some important limitations of the Mauer study that cannot be ignored.  First, only 25-40% of patients with diabetes ever develop diabetic nephropathy.  It seems clear that some patients are not prone to develop diabetic nephropathy despite having risk factors such as hypertension and poor glycemic control.  Some studies suggest there are genetic factors that either decrease or increase patient risks for the development of nephropathy in addition to the known clinical risk factors.  So, it is hard to know what to make of the fact that the placebo group showed only a 6% increase in cumulative incidence of abnormal levels of microalbuminuria.  Ideally, the study should have excluded patients who were at little or no risk for the development of nephropathy regardless of blood glucose control and blood pressure.  Of course, there was no way to do that.

Also, I wonder whether the investigators should have looked at their data with regard to patients’ levels of glycemic control?   The only A1c data in the study were baseline A1cs in the three treatment groups to show that the groups were similar at baseline in terms of glycemic control.  We already know that the level of HbA1c is a strong risk predictor for the development/progression of diabetic nephropathy.  Maybe the A1c trumps the effects of the ACE inhibitor; perhaps the ACE inhibitor is not protective unless the A1c is low?

So, for now I would recommend using an ACE inhibitor as a first line choice for treating hypertension in a patient with diabetes.  I would not, however (and never did) consider using ACE inhibitors to prevent the development of diabetic nephropathy.  I am still undecided whether to recommend an ACE inhibitor to a patient with abnormal and steadily increasing levels of microalbuminuria.  Of course, what complicates all of this are the Mauer study data on diabetic retinopathy; maybe the new dogma will be that ACE inhibitors should be used in all patients with diabetes to prevent/slow progression of diabetic retinopathy?  Most important, we should not forget the old dogma which still stands- glycemic control and blood pressure are both proven powerful risk factors for the development/progression of all diabetic complications.  If one “covers” all the risk factors for diabetic complications, there is no need to debate whether ACE inhibitors help or not.

Using the A1c test as a measure of the degree to which a patient’s diabetes care is being managed optimally

In previous entries, I have discussed the importance of hemoglobin A1c measurements, often called “the A1c test,”  in quantifying  blood glucose control in people with diabetes.  The A1c test is a tremendous advance in diabetes.  As recently as the early 1980s, physicians really had no objective way to assess long-term blood glucose levels in patients.  Patients could do fingerstick blood glucose testing at home on a regular basis which helped give both patients and physicians some idea of how things were going.   But it was not until the  A1c test became widely available AND the Diabetes Control and Complications Trial results showed that the A1c test was a powerful risk predictor for diabetes complications that the wheels of progress started moving fast.

We now know that the A1c test is a reasonably reliable measure of a person’s average blood glucose level over the preceding 3-4 months.  I say “reasonably,” because the test really quantifies a “moving average,” not strictly speaking, an average over time x to time y.  But, even given the test’s limitations as a measure of average blood glucose, it is useful in relating daily patient blood glucose testing to an overall average.  But, where the test really shines is as a very reliable predictor for patient risks of developing and showing progression of all diabetes chronic complications.  Furthermore, the test is more or less standardized among laboratories in the U.S. and most of the result of the world through a National Institutes of Health supported program called “the NGSP.”.  Thus, a simple blood test that requires only a small drop of blood and can be performed in less than 30 minutes can tell a patient and his doctor roughly what the patient’s average blood glucose level has been over the past few months and whether the test result is in a desirable range with respect to risk for the development/progression of diabetes complications.  The test has been used not only for routine patient care but also in quality assurance programs.  So the point I want to make here is that we now have a tool that lets us quantify how well a patient is doing overall with their diabetes care.

What do A1c test numbers mean?

With respect to interpreting A1c test results, I would consider a level of 4-6% as normal (in my laboratory, the upper limit of normal is actually 5.7%).  The American Diabetes Association (ADA) has recommended that patients with diabeetes aim for levels <7% (an A1c of 7% reflects an average blood glucose of about 150-170 mg/dl, with normal about 70-100 mg/dl).  The ADA used to recommend that most people with diabetes maintain A1c levels <8% with higher levels requiring “action.”  I was disappointed when, several years ago, the ADA abandoned this care goal recommendation.  Many patients with diabetes simply cannot achieve A1c levels <7%.  It is my opinion that having a single care goal that many people cannot achieve is not the way to help patients achieve care goals.  An A1c test result of 7.9% (i.e., <8%) reflects an average blood glucose of about 180-200 mg/dl.  Data from the DCCT/EDIC and the UKPDS show that patients’ risks of developing diabetes complications are quite low if the A1c level is maintained at <8% long-term, but not as low in patients whose levels are <7%.  Anyway, that’s what the numbers mean.  In my discussions I will define “optimal control” as levels <7% and “acceptable control” as levels <8%.  But it is important to remember that lower is always better unless the patient is having frequent episodes of hypoglycemia (low blood glucose levels).  In fact, a drop in A1c from 10% to 9% decreases risks for complications much more than a drop from 9% to 8%, which in turn decreases risks more than a drop from 8% to 7%.  This means that for some patients unable to achieve A1c levels in the desirable range, we as health care givers should be willing to applaud any improvements that the patient makes.  This doesn’t mean we (patients and health care givers) should be satisfied with A1c levels that are above desirable levels, but rather, accept that incremental improvements are better than no improvements.

What do we know about the relationship between the quality of diabetes care and the risks for developing chronic complications of the disease?

First, long-term studies such as the Diabetes Control and Complications trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and the United Kingdom Prospective Diabetes Study(UKPDS) have shown clearly that development and progression of all major diabetes complications are strongly related to 3 factors- blood glucose control, blood pressure, and blood lipid levels.  So, simply put, the risk factors for diabetes complications are blood glucose levels, blood pressure levels, and cholesterol levels.  These risk factors are all controllable; hence, in 2009 it is possible to have diabetes, and with proper treatment, be at little or no risk of developing diabetes complications.  That is good news indeed.  Unfortunately, what is possible, is not happening for many people with diabetes; diabetes remains a leading cause of vision loss, nerve damage, kidney failure, and heart disease.

How can we tell if a person with diabetes is actually doing well in managing the condition?

It’s pretty easy for a physician to assess how well people with diabetes are doing in terms of the known risk factors for the development/progression of diabetes complications.  First, just measuring the blood pressure covers that risk factor.  Second, just measuring blood lipid levels covers another major risk factor.  Typically, physicians order a fasting lipid profile which measures blood cholesterol, tryglycerides, LDL-cholesterol (“bad” cholesterol), and HDL-cholesterol (“good” cholesterol).  Third, physicians can assess blood glucose levels by ordering  hemoglobin A1c (also called the A1c test).  The A1c test measures the amount of glucose attached to a person’s red blood cells, which is directly related to the average blood glucose level over the previous 3-4 months.  This test has been shown to be a powerful risk predictor for the development and progression of all diabetes complications (you might want to check out some of my previous entries that discuss this test in great detail).  In summary, all it takes is a stethoscope, a blood pressure cuff, and a bit of blood to assess/monitor risks for the development/progression of all diabetes complications.

Measuring risk vs. doing something about it

So, it’s quite easy to assess how well a person with diabetes is doing in terms of their risk for developing this or that diabetes conmplication.  It’s quite another thing to actually modify (i.e., decrease) a person’s risk factors once it has been determined that risks for this or that complication are increased.  For blood pressure and lipids, assuming the patient will remember to take a pill reliably (and can afford the medication), improving risks is easy.  For blood glucose control it’s not so simple since the solution generally requires that patients make changes in the way they manage their diabetes.  This is the area that I want to focus on in my next entry.