What's New in Diabetes? - November 2003
DEFINITION: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
CLASSIFICATION: The ADA recommends the use of disease etiology rather than the type of pharmacological treatment used in management. Eliminate the terms IDDM and NIDDM and use Type 1 and Type 2.
Type 1: Encompasses the vast majority of cases that are primarily due to pancreatic islet ß-cell destruction and are prone to ketoacidosis. Either autoimmune with a positive antibody (islet cell, GAD65, IA-2, IA-2ß, or insulin autoantibodies) or idiopathic (negative antibodies, etiology unknown). Does not include forms of ß-cell destruction or failure for which non-autoimmune-specific causes can be assigned (e.g., cystic fibrosis).
Type 2: The most prevalent form of diabetes (9 times more prevalent than Type 1), due to insulin resistance with an insulin secretory defect.
Other: Includes MODY (Maturity Onset Diabetes of the Youth) types 1, 2, & 3, pancreatic trauma, infection, tumors, or CF, and drug-induced (e.g. steroids, dilantin, and thiazides).
GDM: Gestational DM develops or is first recognized during pregnancy. The current recommendation is for selective rather than universal screening during pregnancy.
INCIDENCE: Type 1: An estimated 850,000 to 1.7 million Americans have Type 1 diabetes. Of those, about 125,000 are 19 and under. An additional 30,000 Americans develop Type 1 diabetes every year, 13,000 of whom are children.
Type 2: is much more prevalent, with an estimated 16 million Americans having Type 2. Millions of people with type 2 diabetes have not yet been diagnosed.
SCREENING: for Type 2 is a subject of debate. The current recommendation is to screen children over age 10 (or as early as puberty begins) who are overweight (BMI 85th percentile for age and sex, weight for height 85th percentile, or weight 120% of ideal for height) AND have any two of the following risk factors:
1- Family history of type 2 diabetes in first- or second-degree relative
2- Race/ethnicity (American Indian, African-American, Hispanic, Asian/Pacific Islander)
3- Signs of insulin resistance or conditions associated with insulin resistance such as acanthosis nigricans, hypertension, dyslipidemia, or PCOS (polycystic ovary syndrome).
The preferred test is fasting plasma glucose, although an OGTT may be more sensitive.
DIAGNOSIS CRITERIA:
Fasting Plasma Glucose greater than or equal to 126 mg/dl (normal <110), or
Random Plasma Glucose greater than or equal to 200 mg/dl WITH symptoms, or
2-hr Plasma Glucose (on OGTT) greater than or equal to 200 mg/dl (normal <140).
In the absence of unequivocal hyperglycemia with acute metabolic decompensation, one of these three tests should be used on a different day to confirm the diagnosis. Values between normal and diagnostic are considered indicative of Impaired Glucose Homeostasis (pre-diabetes).
MANAGEMENT: Since the Diabetes Control and Complications Trial (DCCT) in 1981, it has been well established that “tight control” starting in pre-pubertal ages is essential to prevent long-term complications. Suboptimal blood glucose control has a lasting harmful effect even if control improves later. Intensive insulin therapy to minimize hyperglycemia is recommended for all patients with type 1 diabetes.
More individualized and physiological therapy is now possible. Continuous blood glucose monitoring reveals postprandial hyperglycemia and asymptomatic nocturnal hypoglycemia and may be especially useful for programming overnight basal insulin rates for pump therapy. These devices are used only in diabetes centers which lend them to patients. Rapid-acting (Lispro and Aspart) and long-acting (Glargine) insulin analogs offer more physiological insulin profiles than traditional insulin preparations.
Type 1: Intensive diabetes management: Both continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection therapy are effective means of implementing intensive diabetes management with the goal of achieving near-normal levels of blood glucose and improved lifestyle flexibility.
The limiting factor preventing ideal glycemic control remains hypoglycemia. Glucagon secretion is blunted early in the course of type 1 diabetes, increasing the patient’s vulnerability to hypoglycemia. Furthermore, the blood glucose threshold for release of catecholamines, which both stimulate glucose production and produce warning symptoms such as sweating and trembling in response to hypoglycemia, is lowered in patients with better glycemic control, even more so during sleep. Continuous glucose monitoring devices, the new insulin analogs and continuous subcutaneous insulin therapy hold promise of improving control without the attendant risk of hypoglycemia.
Glargine is a long acting (12-24 hr), presumably peakless insulin that is rapidly replacing other long and intermediate acting insulins in children. Detemir is an experimental insulin with an added fatty acid chain, which enhances binding to albumin. Short acting and rapid insulins (Lispro and Aspart) are now standard instead of regular insulin in most children.
Tight control requires at least 4-6 injections/day. CHO counting is essential for achieving tight control since insulin doses are adjusted based on blood sugar and carbohydrate (CHO) intake. Ideally, CSII (pump) therapy should be considered within the first year after diagnosis. Use of CSII requires care by skilled professionals, careful patient selection and monitoring and thorough patient education. These pumps provide lifestyle flexibility, particularly for meal schedules and travel but may be too demanding for some. Candidates must be strongly motivated and willing to work with their health care provider in assuming substantial responsibility for their day-to-day care.
Screening for associated disease: Principally thyroid and Celiac disease are more common in children with Type 1 DM. Initial screen at diagnosis with TSH, T4, and anti-endomysial antibodies. Frequency of further testing is debatable.
Islet transplant: promising but remains experimental will be a while before it becomes standard.
Inhaled insulin: still experimental but Phase III trial is completed and appears very effective. Principal use will be in Type 2.
Non-invasive blood glucose monitoring: Frequent automatic glucose readings can be obtained non-invasively through the reverse iontophoresis, in which a low electric current pulls glucose molecules through the skin for collection in a gel disc. A wristwatch –like device is worn and is approved for patients over 7 years. Its cost (about $1000 for the device and more than $100 per disposable 12-hour sensor) limits widespread use.
Type 2: Prevention, prevention, prevention, behavioral modification. A whole different subject, but suffices to say that 10 minute activity “bouts” 3 times/day will greatly improve metabolic homeostasis. But when all fails, medications can be introduced, keeping in mind that only Metformin and insulin are approved for use in children. In Type 2, management should change with disease progression; introduction of insulin should not be delayed if metabolic control becomes suboptimal.
Increase insulin sensitivity: Early in the disease process, the aim should be to target insulin resistance with diet and exercise plus metformin therapy. A weight loss of 5 kg leads to a 25%–50% reduction in insulin resistance. Metformin is tolerated by most patients if started at a low dose and slowly increased. The thiazolidinediones (rosiglitazone and pioglitazone) are newer insulin-sensitizing agents which are effective, but have the disadvantage of causing some weight gain and fluid retention. Unlike metformin, they are safe in patients with renal impairment.
Increase circulating insulin: If strategies to increase insulin sensitivity are ineffective, the next step is to increase circulating insulin level. Available oral agents are the sulfonylureas and the glitinides. Metformin should be continued in obese patients.
As sulfonylureas are potent and long-acting, hypoglycemia is a potential side effect, but can be avoided with careful dose titration. Sulfonylureas also cause weight gain in most patients and lose efficacy with time.
Glitinides (e.g., repaglinide) are short-acting drugs that increase insulin secretion. They are well tolerated but less potent and cause less hypoglycemia.
Exogenous insulin: If diabetic control remains, or becomes, suboptimal on oral combination therapy, then insulin is indicated.