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Type 2 Diabetes
Written by Jeffrey R. Waggoner, MD   

Type 2 diabetes is caused by peripheral insulin resistance with an insulin-secretory abnormality that varies in severity. Both abnormalities must be present for Type 2 diabetes to develop, i.e. all obese patients have a degree of insulin resistance but only those who cannot increase beta-cell production of insulin will develop diabetes.

Clinical Characteristics of Type 2 diabetes

90% of patients with Type 2 diabetes are obese. As patients progress from normal glucose tolerance to abnormal glucose tolerance, the first glucose levels that become elevated are postprandial (after meals). As inhibition of hepatic gluconeogenesis declines, fasting hyperglycemia also increases.

Type 2 diabetics will usually retain some ability to synthesize insulin — as opposed to type 1 diabetics. Thus even though severe type 2 diabetics may be using insulin as an adjunct or instead of oral hypoglycemic agents, its withdrawal will not produce ketoacidosis. It is also true that most type 2 diabetics will return to normal with weight loss. (1)

Metabolic syndrome leads to Type 2 diabetes

Metabolic syndrome or syndrome X is a condition characterized by increased amounts of abdominal fat that causes at least 2 of the 3 problems—insulin resistance, hypertension, and dyslipidemia. The theory is that increased fat causes to increased fatty acids in the portal vein, resulting in fat in hepatocytes and muscle cells. This leads to a resultant insulin resistance, hyperinsulinemia, and eventually Type 2 diabetes—and all of its concomitant sequelae. (2)

Atypical subsets of Type 2 diabetes

Maturity-onset diabetes of the young

There is a subset of Type 2 diabetes called maturity-onset diabetes of the young (MODY). This affects many generations of the same family. It has an onset in patients younger than 25 years. There are several types of MODY, and some of the responsible genes may be detected with widely available assays.

Gestational diabetes

Gestational diabetes (GDM) is present in approximately 4% of all U.S. pregnancies. If untreated, it can have profound intranatal complications including macrosomia, hypoglycemia, hypocalcemia, and hyperbilirubinemia. It is defined as any degree of glucose intolerance with first recognition of pregnancy. (1)

National Guidelines for managing Type 2 diabetes

Initial evaluation

National guidelines call for initial evaluation of patients who are potentially diabetic to include either a fasting plasma glucose, casual plasma glucose or a glucose tolerance test, a urine for ketones, and a general medical assessment.

Treatment and follow up planning

National guidelines also call for a staged treatment program, an established monitoring program using self monitored glucose levels, and a followup program that includes hemoglobin A1c, lipid levels, blood pressure monitoring and treatment, monitoring of renal function, appropriate immunizations, full histories and physicals, and nutritional and diabetic counseling as is appropriate. Because of the wide range of sequelea, it is important to have an active plan for complication surveillance, and providing psychosocial counseling as needed. (3)

Staged Treatment

Initial stage

The staged treatment called for by national guidelines begins with attempts at ''weight loss and increase in exercise''. Following, or in addition to, this intervention, ''pharmacologic monotherapy'' should be initiated with one of the agents from the different classes of oral hypoglycemic agents.

Metformin is the first line choice of medication. Alternative choices are a member of the thiazolidinediones class, followed by sulfonylureas, meglitinide analogues, and glucosidase inhibitors.

Second stage

The next stage is a combination of oral agents. The goal is to combine those medications that have a different mechanism of action, thus creating a synergistic effect. Guidelines call for an initial use of a sulfonylurea plus metformin, or a meglitinide analogue, or a glucosidase inhibitor.

Second choice is metformin plus a sulfonylurea, or a meglitinide analogue, or a thiazolidinedione or a glucosidase inhibitor. This is followed by a thiazolidinedione plus a sulfonylurea or metformin.

Final stage

The final stage is the staged addition of insulin—monotherapy or combined with oral agents. Guidelines begin with Lispro or Aspart, then regular human insulin, neutral protamine Hagedorn (NPH) insulin, Glarine, and Lente insulin.

Quite obviously, the latitude of this staged therapy is enormous — one of the reasons that attention to compliance, patient education, and appropriate follow up are crucial in any successful treatment program. However, this latitude should not include haphazard jumps from one combination to another. It should be done with an overlying and well defined rationale. (3)

References

1. Votey, S.R. and Peters, A.L. Diabetes Mellitus, Type 2 - A Review. 2008 Emedicine.com

2. http://www.merck.com/mmpe/sec01/ch006/ch006b.html

3. Type 2 Diabetes practice guidelines. National Guideline Clearinghouse.

 
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