The ABCs of Diabetes: A Lecture Outline

I will be giving a lecture to the Family and Community Medicine Department resident physicians at the University of Missouri Health Sciences Center in a few days.  I thought I would post the lecture outline which includes what I think are important references about diabetes care.  It is interesting that in preparing the talk, I looked over some of my notes from previous talks to the same group.  The oldest talk was in 1979 and the most recent, in 2009.  I was surprised how little things have changed over the past decade in terms of new and important information on diabetes patient care.  Maybe that’s because we made so much progress in the 1980s and 90s?  Anyway, I was a bit surprised.  I do have one minor correction to make to the outline- in the table on medications for patients with type 2 diabetes, just the other day, the FDA rejected the drug dapagliflozin, a sodium-coupled glucose co-transporter inhibitor (see reference 22).  I don’t know why the drug did not get FDA approval but I suspect it was because of so little long-term data on side-effects.

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)

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