Long-Term Normoglycemic Remission in Black Newly Diagnosed NIDDM Subjects

Abstract

We have defined and characterized the natural history of spontaneous near-normoglycemic remission off of antidiabetic medication in 79 black NIDDM subjects. They had initially presented with plasma glucose levels of 37.8 +/- 19.3 mmol/l. Baseline clinical metabolic and 8-year prospective data were obtained (51 men and 28 women, mean age 45 +/- 10 years, islet-cell or GAD antibody negative). After hospitalization and intensive outpatient treatment, near-normoglycemic remission (fasting plasma glucose 6.1 +/- 0.83 mmol/l and HbA1c 0.95 +/- 0.10 of upper limit of normal) occurred within 8 +/- 10 months of insulin or sulfonylurea therapy. This was unrelated to the resolution of stress or significant weight loss (1.9 +/- 4.97 kg). Metabolic studies performed during remission showed 17% normal, 33% impaired, and 50% diabetic glucose tolerance. Glucose disposal (1 mU x kg-1 x min-1) euglycemic insulin clamp with D-[3(-3)H]glucose) was higher in the normal glucose tolerance group compared with the impaired and diabetic groups (37.8 +/- 10.2 vs. 26.1 +/- 10.7 and 26.7 +/- 12.0 micromol x kg-1 x min-1; P < 0.05) despite similar BMIs in all three groups (28.8 +/- 3.7 kg/m2). Insulin secretion was below the normal range. Of 79 patients, 27 relapsed. A Kaplan-Meier survival analysis gives a median time of 40 months to relapse. Higher presenting plasma glucose and male sex predicted earlier relapse. Near-normoglycemic remission may occur in up to 30% of black new-onset NIDDM patients. It appears to be associated with intensive initial glycemic regulation and may be a method of decreasing the development of microvascular complications in NIDDM.

Short duration of diabetes and disuse of sulfonylurea have any association with insulin cessation of the patients with type 2 diabetes in a clinical setting in Japan (JDDM 30)

“…Logistic regression analysis also revealed that the duration of diabetes had significant association with a cessation of insulin therapy. This finding, together with results from other studies [13][14][15], indicates that a shorter duration of diabetes may be one of the associated factors with insulin cessation. It has been reported that, at the onset of T2DM, the total pancreatic β-cell mass is already decreased to almost half [16] and that β-cell function declines at a constant rate after the onset of diabetes [17].…”

“…It is difficult to say whether this rate of cessation of insulin therapy is high or low, because only a few studies have investigated remission rates after the initiation of insulin therapy in T2DM patients, and these studies were performed in different settings to that of the present study [13][14][15].…”

Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes

“…This form of diabetes is a common clinical presentation involving ϳ50% of adult African Americans (and, increasingly, Hispanic and Native Americans) with obesity and newly diagnosed diabetes who present with ketosis and/or severe hyperglycemia. Although these patients are severely insulin resistant and insulinopenic on presentation, with intensive insulin therapy the majority of patients achieve near-normoglycemic remission within ϳ10 -12 wk, become more insulin sensitive, and do not require exogenous insulin (1,33,44). Therefore, an analysis of muscle Akt activation in these patients at presentation and remission provides an ideal opportunity to examine the association of hyperglycemia with Akt isoform activation.…”

Adult-Onset Atypical (Type 1) Diabetes

“…Recently, some authors have described this subcategory in other ethnic groups, such as Native Americans and Hispanic Americans (5). The initial manifestation of the diabetes in these cases may be ketoacidosis similar to type 1A diabetes, although the course of the disease is unusual as insulin therapy is initially needed to maintain metabolic control and, after a variable period of time (usually within months), good control can be achieved with either diet or oral agents (5)(6)(7)(8)(9). On the other hand, these patients differ from those with type 1A diabetes because their physical characteristics are more typical of patients with type 2 diabetes; they are often obese or overweight at the time of diagnosis and, in most of the cases, there is a family history of type 2 diabetes (5).…”