Remission in Diabetes

African American subjects with Type 2 diabetes who present with severe hyperglycemia may develop long-lasting remissions (92, 93). At the time of presentation, these individuals require hospitalization for severe symptomatic hypergly-cemia (mean glucose 600 mg/dl, 33.3 mM) and following a period of treatment, with anti-diabetic pharmacologic agents they are able to discontinue these agents and remain in near normoglycemic remission with normal HbAlC levels. They are able to maintain this for years on their own version of a 'diet' including occasional icecream, cake and barbecue (92, 94-99).

The development of remission is not associated with: (1) marked weight loss; (2) reversal of stressful illness; or (3) a 'transient honeymoon', or variant of immunologically mediated Type 1 diabetes as evidenced by absent islet cell and glutamic acid decarboxylase antibodies (92).

The clinical characteristics of 72 individuals who developed remission were: mean age 48 years, BMI 27.6 kg/m2 (range 21-35); two-thirds were men. All had newly diagnosed Type 2 diabetes and remission developed within 12 months. Most patients participated in intensive glycemic monitoring and regulation. Although the hemoglobin AlC was within normal range and mean fasting plasma glucoses were 110 mg/dl (6.1 mmol/l), oral glucose tolerance testing showed that 36/72 (50%) had a diabetic glucose tolerance test (2 hour plasma glucose 239 mg/dl or 13.3 mmol/l), 24/72 (33%) had impaired glucose tolerance and 12/72 (25%) had normal glucose tolerance. Nearly all the individuals with normal glucose tolerance were insulin-sensitive, whereas only half of those with diabetic or impaired glucose tolerance were insulin-sensitive, using the euglycemic insulin clamp technique.

Long-term follow-up of 8 years showed that remission was maintained for a median of 40 months or 3.3 years (Figure 9A.6) (93). A small separate subset have been in remission for 10-15 years. Additionally, once in remission, the usual medical or surgical 'stresses' did not perturb glucose homeostasis and precipitate a relapse to hyperglycemia.

To determine whether remission could be prolonged with low doses of pharmacologic agents, a small double-blind placebo-controlled study was performed: treatment with glipizide (1.25-2.5 mg/ day) for 3.5 years significantly prolonged the duration of remission compared to placebo (100).

To determine the frequency of remission, all newly diagnosed Type 2 diabetes subjects hospitalized with symptomatic hyperglycemia over 300 mg/dl (16.7 mmol/l), were treated intensively after discharge with multiple doses of insulin, diet and diabetes education. The hypothesis was that intensive glycemic regulation would reverse any element of glucose toxicity and potentially allow

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