Introduction

Diabetes mellitus (DM) is a complex of disorders that result in hyperglycemia. Insufficient insulin production and/or resistance to the effects of insulin cause the hyperglycemia. Without the effect of insulin, the cells of the liver and skeletal muscle are unable to efficiently remove and store excess blood glucose. While diet and exercise can modify blood glucose, without effect of insulin blood glucose remains abnormally high in the feeding and non-feeding states.

There are three main types of DM: 1) type 1 diabetes, 2) type 2 diabetes and 3) gestational diabetes.

  1. Type 1 diabetes (T1D) is usually caused by an autoimmune reaction that destroys the insulin secreting pancreatic β-cells. The loss of β-cells results in an absolute insulin deficiency.
  2. Type 2 diabetes (T2D) is characterized by inadequate insulin secretion in conjunction with cellular resistance to the effects of insulin.
  3. Gestational diabetes tends to occur around the 24th week of pregnancy. The condition is believed to result from a resistance to insulin probably caused by hormones produced by the placenta.

Chronic hyperglycemia of DM is a leading cause of cardiovascular disease, blindness, kidney failure, and lower-limb amputation. The prevalence of DM is increasing in the United States. The 2014 National Diabetes Information Clearinghouse (NDIC) reported the following statistics:

The diagnosis and prognosis of diabetes may be determined by plasma glucose and hemoglobin A1C levels. Plasma glucose measures blood glucose at a single point in time. The A1C test provides an estimate of exposure to glucose over months.

Adult Diabetes Diagnostic Tests and Results
  A1C Fasting=0 cal/8hr 2 hr/post 75g oral glucose tolerance test
Normal 4% to 5.6% <99 mg/dL <139 mg/dL
Pre-diabetes 5.7 to 6.4% 100 to 125mg/dL 140 to 199mg/dL
Diabetes >6.5% >126mg/dL >200mg/dL
       

The natural life of a red blood cell is about three months. A1C is the portion (%) of hemoglobin A that has been irreversibly glycosylated in blood cells from exposure to plasma glucose over the preceding months.

A1C is approved to diagnose T2D and prediabetes but is not recommended for diagnosis of T1D or gestational diabetes. A1C results may be unreliable when the sample hemoglobin is abnormal. Sickle cell anemia or a thalassemia genetic markers may increase the risk of an unreliable A1C result.

The American Diabetes Association recommends an A1C goal for adults with diabetes is 7 percent but more or less stringent control may be appropriate for some individuals. An A1C of 7 equates to about 154mg/dL reported by a self-monitoring meter.

The majority of diabetes patients are unable to achieve and sustain the recommended A1C goals through intensive education and lifestyle changes alone. However, new classes of medications, blood glucose self-monitoring, new delivery devices and recombinant human insulin have radically improved and extended the lives of T2D and T1D diabetics.

In addition there is clinical evidence that intensive (basal/bolus) insulin therapy for T1D can reduce the microvascular and macrovascular complications associated with long-term diabetes.  Short-term intensive insulin therapy appears to improve pancreatic β-cell function for some patients when administered early in the course of T2D.



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