Multitissue Insulin Resistance Despite Near-Normoglycemic Remission in Africans With Ketosis-Prone Diabetes

Abstract

African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU ⅐ m Ϫ2 body surface ⅐ min Ϫ1 and 80 mU ⅐ m Ϫ2 ⅐ min Ϫ1 insulin infusion rates) euglycemic clamp with [6,6-2 H 2 ]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test.RESULTS -The total glucose disposal was reduced in patients compared with control subjects (7.5 Ϯ 0.8 [mean Ϯ SE] vs. 10.5 Ϯ 0.9 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ; P ϭ 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 Ϯ 0.3 vs. 3.0 Ϯ 0.1 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ; P ϭ 0.001) and after 200-min insulin infusion (10 mU ⅐ m Ϫ2 ⅐ min Ϫ1 : 1.6 Ϯ 0.2 vs. 0.6 Ϯ 0.1, P ϭ 0.004; 80 mU ⅐ m Ϫ2 ⅐ min Ϫ1 : 0.3 Ϯ 0.1 vs. 0 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P ϭ 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 Ϯ 161.4 vs. 1,230.0 Ϯ 174.1 mol/l; P ϭ 0.002) and remained higher after 100-min 10 mU ⅐ m Ϫ2 ⅐ min Ϫ1 insulin infusion (706.6 Ϯ 96.5 vs. 381.6 Ϯ 55.9 mol/l; P ϭ 0.015).CONCLUSIONS -The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.

Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises

“…The period of near-normoglycemia remission is variable, with some studies reporting remission lasting between 6 and 120 months (10,13). Despite the initial improvement, most obese African American patients with DKA and severe hyperglycemia (12,16) have a gradual decline in their β-cell function (10) with continued insulin resistance (15) if treated with diet alone. Previous studies with sulfonylureas showed prolongation of near-normoglycemia remission in obese African American patients with an initial presentation of DKA and severe hyperglycemia (12,16), but sulfonylurea treatment may increase the risk for hypoglycemia and weight gain.…”

“…Despite significant improvement in insulin secretion and insulin action at the time of remission from insulin (1,14,15), many patients experience recurrence of hyperglycemia if treated with diet alone (10). Few studies have focused on the optimal treatment to prolong the period of near-normoglycemia remission in obese African American patients with DKA and severe hyperglycemia.…”

Diabetic ketoacidosis: not always due to type 1 diabetes

“…11 As with type 1 diabetes, exogenous insulin is needed to treat the ketoacidosis. However, once the acute metabolic derangement of hyperglycaemia and accelerated lipolysis (the cause of the ketosis) is reversed with insulin, both β cell function and insulin sensitivity improve.…”

Ketosis-Prone Atypical Diabetes: Glucagon Is There, Too

“…At the onset, KPD often appears as type 1 diabetes with acute hyperglycemia and ketosis or ketoacidosis and the obvious need for insulin therapy but the signs of autoimmunity against islet β-cells are absent. In contrast, during near-normoglycemic remission, patients with KPD usually display multisite insulin resistance similar to that seen in type 2 diabetes (4,5). In 2008, Sobngwi et al (6) hypothesized that KPD is a subtype of type 2 diabetes with acute onset at diagnosis as the result of an environmental factor such as a human herpes virus infection that would severely impair glucose-stimulated insulin secretion and favor ketogenesis.…”